Archive for the ‘Alzheimer’s’ Category

What Causes Alzheimer’s? Not Toxic Amyloid, New Study Suggests

What causes Alzheimer’s? Not toxic amyloid, new study suggests

Many researchers have argued that the accumulation of toxic beta-amyloid in the brain causes Alzheimer’s. However, a new study offers some evidence contradicting this sequence.

researcher assessing brain scan
New research is questioning the predominant hypothesis that a buildup of beta-amyloid causes Alzheimer’s disease.

Alzheimer’s disease affects over 5.5 million people in the United States and millions more around the globe.

Yet, researchers are still at a loss as to why this condition — which is characterized by memory impairment and many other cognitive problems — occurs in the first place. And until they fully understand the cause, investigators will remain unable to devise a cure.

So far, the prevailing hypothesis among experts has been that the excessive accumulation of a potentially toxic protein — beta-amyloid — in the brain causes Alzheimer’s.

Researchers have argued that beta-amyloid plaques disrupt the communication between brain cells, potentially leading to cognitive function problems.

Now, a new study from the University of California San Diego School of Medicine and the Veterans Affairs San Diego Healthcare System suggests that while the buildup of beta-amyloid has associations with Alzheimer’s, it may not actually cause the condition.

In a study paper that appears in the journal Neurology, the researchers explain what led them to reach this conclusion.

“The scientific community has long thought that amyloid drives the neurodegeneration and cognitive impairment associated with Alzheimer’s disease,” says senior author Prof. Mark Bondi.

He notes that “[t]hese findings, in addition to other work in our lab, suggest that this is likely not the case for everyone and that sensitive neuropsychological measurement strategies capture subtle cognitive changes much earlier in the disease process than previously thought possible.”

What comes first?

In their study, the researchers worked with a total of 747 participants with different levels of cognitive health. All of the study participants agreed to undergo neuropsychological assessments, as well as PET and MRI brain scans.

Of the participants, 305 were cognitively healthy, 289 had mild cognitive impairment, and 153 displayed markers of what the investigators call “objectively-defined subtle cognitive difficulties (Obj-SCD).”

Experts define mild cognitive impairment as a state of cognitive impairment that is more severe than what one would normally experience with age, but not yet severe enough for a dementiadiagnosis.

However, mild cognitive impairment does develop into dementia in a significant number of people.

But what are Obj-SCD? In their paper, the investigators define them as “difficulties or inefficiencies on some sensitive cognitive tasks even though the overall neuropsychological profile is in the normal range.”

That is, they are a measurement of experienced, subtle cognitive functioning problems that occur in the absence of any visible signs of brain or psychological issues. To find out whether someone is experiencing Obj-SCD, researchers assess, among other factors, how efficiently that person can learn and retain new information.

Previous research has suggested that individuals with Obj-SCD are at a higher risk of mild cognitive impairment and forms of dementia.

In the current study, Prof. Bondi and the team found that beta-amyloid built up at a faster rate in the participants with Obj-SCD compared with those who were deemed cognitively healthy. Moreover, brain scans of people with Obj-SCD showed that these individuals experienced a thinning of brain matter in a region called the entorhinal cortex.

Past research has shown that the entorhinal cortex decreases in volume in people with Alzheimer’s disease. This is significant because this brain region plays a role in memory and spatial orientation.

The researchers also found that while people with mild cognitive impairment had higher quantities of beta-amyloid in their brains at the beginning of the study, this protein did not seem to build up any faster in these participants than it did in cognitively healthy individuals.

But why do the current findings potentially contradict a decades-old hypothesis about the development of Alzheimer’s? Prof. Bondi explains:

This work […] suggests that cognitive changes may be occurring before significant levels of amyloid have accumulated. It seems like we may need to focus on treatment targets of pathologies other than amyloid, such as tau, that are more highly associated with the thinking and memory difficulties that impact people’s lives.”

“While the emergence of biomarkers of Alzheimer’s disease has revolutionized research and our understanding of how the disease progresses, many of these biomarkers continue to be highly expensive, inaccessible for clinical use, or not available to those with certain medical conditions,” adds first author Kelsey Thomas, Ph.D.

The new study’s findings could help change that by refocusing the research approach on more subtle markers of Alzheimer’s, such as those assessing for Obj-SCD.

“A method of identifying individuals at risk for progression to [Alzheimer’s disease] using neuropsychological measures has the potential to improve early detection in those who may otherwise not be eligible for more expensive or invasive screening,” says Thomas.


The Maddening Saga of How an Alzheimer’s ‘Cabal’ Thwarted Progress Toward a Cure For Decades

The maddening saga of how an Alzheimer’s ‘cabal’ thwarted progress toward a cure for decades


I posted on this a year ago when Leslie Norins, Ph.D. wrote this fantastic paper:

Alzheimer’s has had a Cabal similarly to Lyme in that research has been hijacked by a group of individuals with blinders on.  According to Norins, the 2017 Alzheimer’s Association had a conference in London where researchers from 70 countries could share progress.  A keyword index of the presentations showed the largest entries, 110, were for amyloid/APP.The next most common item was tau, the tangled protein, with 85 entries. Inflammation—the body’s reaction to something—had 45 mentions.  Presentations of germ importance had only single digit presence: prion proteins (8 entries), infectious disease (4 entries), bacteria (1 entry). Virus was not even listed as a keyword.

Yet numerous researchers have doggedly fought against the myopic focus and have found spirochetes in the brains of Alzheimer’s patients:, and Kris Kristofferson was diagnosed with Alzheimer’s but actually had Lyme disease:  Fantastic read by microbiologist Tom Grier.

A Turning Point in Alzheimer’s Disease: Microbes Matter

A Turning Point in Alzheimer’s Disease: Microbes Matter

For those interested in infectious agents and Alzheimer’s disease (AD), this year’s Alzheimer’s Association International Conference (AAIC) represented a landmark in that the Alzheimer’s Association, the second leading provider of funding for research on the disease, and the organizer of the largest AD conference in the world, organized with enthusiasm a session comprising a discussion on infectious agents and AD. This was the first time that the word ‘viruses’, and probably the first time ‘bacteria’ too, had been heard at a major session of an Alzheimer’s Association conference. Gratifyingly, Dr. Maria Carillo, chief science officer of the Alzheimer’s Association, made a declaration of support for furthering research on this topic, stating that “Ideas in this area of research are still evolving; there is now growing evidence that microbes1 such as bacteria and viruses may play a role in degenerative brain diseases such as Alzheimer’s.” She emphasized that

“new research suggests infectious agents may be triggering immune reactions related to plaques and tangles …  and that loss of cognitive function in Alzheimer’s disease may stem from several different disease processes in the brain, not just one”.

Five talks were arranged for the infection-AD session: three of the speakers supporting a role for microbes and two opposing it. The talks were (in theory) restricted to 10 minutes each, which obviously allowed only the briefest presentation of evidence for or against a microbial role, and precluded that of any new, unpublished work.

The first talk, by Rob Moir (Massachusetts General Hospital and Harvard Medical School), started with a reminder of the eponymous Dr. Alois Alzheimer and his seminal observations on the unusual features of a previously unrecognized disease of the brain. Moir stated the main objections that have been raised to the concept that amyloid-β (Aβ) is an antimicrobial peptide (AMP) produced to combat infection—and then demolished them. The first objection was that that the current amyloidogenesis concept obviates the need for an infectious agent. His answer to this was that amyloid formation is in fact a response to infection. To the point that no single microbe has been closely associated with the disease, Moir argued that many different types of infection can stimulate amyloidogenesis and that its fibrilization results in its encaging the microbe [1]. (Interestingly, the concept of entrapment of microbes was raised many years ago in the flocculation hypothesis of Robinson and Bishop (2002) [2], but was ignored, as was the discovery a few years later, though ignored to a lesser extent, that most of HSV1 DNA in AD brains is located within amyloid plaques [3].) Moir voiced also that none of us was suggesting that Aβ was unimportant, but instead, that it has indeed a major role in AD, but not as a cause of the disease.

The second talk, by the present author (University of Manchester), gave a more or less potted history of the discoveries that led to the formulation of the HSV1-AD concept; this maintains that HSV1 is likely a major cause of the disease, though the take-home message stressed that the concept does not preclude the likelihood that specific bacteria too are involved in the development of the disease. The slides displayed the evidence for HSV1 presence in brain and its reactivation there, its association with AD, including its causing an accumulation of Aβ and P-tau in infected cell cultures and mouse brain, its co-localization in AD amyloid plaques, and also the protective effects of the antiviral, acyclovir, on HSV1-infected cells in culture [4]. Further, the importance of understanding that infected does not necessarily mean affected—hence the existence of infected, but asymptomatic, “controls”—was stressed. Finally, the striking population epidemiological data from Taiwan were described, showing the association of HSV infection and AD, and the success of antivirals in preventing (or possibly delaying) the disease, the latter result supporting a causal role for HSV1 in AD [5, 6].

The 3rd supportive talk, by Ben Readhead (ASU-Banner, Neurodegenerative Disease Research Center), described the usage of large multiomic next-generation sequencing studies for exploring the role of the brain microbiome in AD, aiming to find whether microbes in the brain were causal, accelerants, or opportunistic. The main discovery of the study was the importance of HHV6 and 7 as well as HSV1 in AD brains, including positive correlations between viral abundance, clinical dementia rating, and neuropathology [7]. (In fact, HHV6 was first detected in AD brains at a much higher frequency than in age-matched controls, in 2002 [8], though its level was not quantified; indeed frequency/prevalence needs to be distinguished from the abundance/level/amount of a microbe, the latter but not the former being reported in the paper by Readhead et al. [7]). The conclusion of Readhead et al. [7] was that virus-host regulatory networks indicate complex interactions between several species of herpesvirus and host genes, including perturbation of host networks related to the pathogenesis of AD; these suggest that infections are at least capable of accelerating disease, and also indicate testable hypotheses for further evaluating the pathogen hypothesis of AD.

The two dissenting voices were then heard, not so much refuting any points raised by the proponents or even the involvement of microbes in AD but instead, questioning the significance of their presence and the possible mechanisms of microbial action. The talk by Todd Golde (University of Florida) stressed the important point, on which all the speakers agreed, that association does not prove causality, and also that some of the studies described were carried out with insufficient care. More importantly, the results might be an indication of “reverse causation”, i.e., neurodegeneration might lead to some degree of reactivation of dormant viruses present (although by saying this, he tacitly acknowledged at least the presence of viruses in brain). However, his main concern was that such research might distract from more impactful work (such as amyloid studies).

The concerns of the last speaker, Michael Heneka (University of Bonn Medical Center), were partly based on the role of microglia, including the likelihood that microbial pyroptosis (a highly inflammatory form of programmed cell death that occurs most often because of infection by intracellular pathogens) seeds the deposition of Aβ [9]. He posited also that bacteria, rather than being involved at the initial stage of AD, might invade the brain during the terminal stage of the disease as a result of local chronic brain inflammation compromising the integrity of the blood-brain barrier. He considered too the possibility that peripheral bacterial infection might accelerate disease pathogenesis without the bacteria actually infiltrating the brain [10]. (In fact, the HSV-AD concept suggests that reactivation of HSV1 existing in brain might well occur as a result of peripheral infections leading to brain inflammation.)

The audience was estimated as some 700 people, filling completely the large auditorium. Whether or not anyone present changed sides because of the arguments is unknown; taking a vote before and after the discussion (as in the Controversies in Neurology congresses) might have revealed that. However, no objections of any type were raised, suggesting that as in the past, there are no true arguments against the putative role of microbes. In fact, the extreme hostility to the concept that existed for almost three decades although ludicrous, as the opponents never voiced any scientific objections, precluded any appreciable funding for the work and caused great difficulties in publication of results. It was therefore gratifying that microbial studies are now described by the AAIC as one of the “currently hot topics in neuroscience”, and also that Dr. Richard Hodes, director of the National Institutes of Health (NIH)’s National Institute on Aging, told STAT (the health-oriented online news produced by Boston Globe Media) [11], “We’ve brought together pharma, biotech, philanthropies, and multiple academic departments to work together to identify new targets for intervention,” and “We’ve learned from the unfortunate failures in this space …  the culture shift is really remarkable …  .” He said of the viral theory that “People thought it was unreasonable, crazy, had no evidence, …  but the level of evidence has reached a point where we think it’s important to research.” Further, at the end of the session, Dr. Mackiewicz, of the National Institutes of Aging (NIA), announced that the NIA had heard the pros and cons of this debate and was of the view that Infectious Etiologies should be a high priority target.

Proof of causality in a non-contagious disease of humans can be provided either by prevention of a disease by a drug that targets specifically the putative agent or, in those already suffering from the disease, by slowing their rate of deterioration, or else by vaccination specifically against the putative agent. A clinical trial of valacyclovir (VCV), the biodrug of acyclovir, is being run by Dr. DP Devanand at the New York State Psychiatric Institute, and colleagues; they hope it will show whether or not VCV reduces the rate of deterioration in HSV1- or HSV2-seropositive patients with mild AD: 65 patients will be treated with oral VCV (2 to 4 g per day) and will be compared with 65 patients with placebo, in a 78-week Phase II proof of concept trial [12]. Assessments at baseline and after 78 weeks will include tests of cognition and activities of daily living (ADAS-Cog and ADCS-ADL), usage of 18F-Florbetapir PET and 18F-MK-6240 imaging to detect amyloid and tau accumulation, changes in cortical thinning on structural MRI, olfactory identification deficits, and antiviral antibody titers. APOE genotypes will be investigated also. The results will not be known until 2022, but it seems wise to stress that if the trial proves negative, and sufferers are helped only minimally or not at all by the antiviral, the HSV1-AD concept would not be disproved: possibly, an anti-inflammatory is needed in combination with the antiviral, or there might be some other factor in the disease that we are currently unaware of, and which, therefore, has not been combated.

A clinical trial supported by the company Cortexyme is investigating treatment for the oral bacterium Porphyromonas gingivalis, the main bacterium involved in the pathogenesis of periodontitis, which has been implicated in AD. P. gingivalis bacteria produce major virulence factors, gingipains, which are cysteine proteases, and the trial is based on the discovery of P. gingivalis DNA in the brains of over 90% of people with AD (consistent with earlier studies detecting the bacterial DNA in brain of infected mice [13]) and the finding that gingipain levels correlate with tau and ubiquitin pathology [14]. Dominy et al. [14] found also that after oral P. gingivalis infection of mice, the bacteria, on entering the brain, caused AD-like changes, including the formation of amyloid plaques, inflammation, and the death of hippocampal neurons. A gingipain inhibitor COR388, produced by Cortexyme, prevented these AD-like changes and was found to be well-tolerated in Phase Ib human studies. Initial results of a large Phase II/III trial supported by Cortexyme will be revealed at the end of 2021.

What of the future? Probably, the most pressing needs are, firstly, data on the type(s) of microbe present in individual brains, so that an appropriate regimen of treatment can be devised, and secondly, detailed mechanisms of viral damage that lead to the development of the disease. Research on microbes and AD has expanded greatly during the last year or so, one or more relevant articles being published every month, and it will expand further in view of the funding that NIH has promised (followed by the American Society for Infectious Diseases). To those of us who endured two or more decades of baseless opposition, it is heartening to read the NIA’s “Notice of Special Interest [which] specifies a high-priority topic of interest”: “Taking into consideration the strong links between microbial pathogens and AD and the emergence of the antimicrobial protection hypothesis of AD, this high-priority topic invites research on mechanisms underpinning neurodegeneration in AD associated with microbial pathogens in the CNS” [15]. One can only hope that funding bodies in other countries will take note of the changing attitudes of US funders, and will open their minds and resources to aspects such as infection. Certainly, the future is starting to look brighter for research on microbes, and hopefully will look brighter also for AD patients and their carers.


The author’s disclosure is available online (




Kumar DKV , Choi HS , Washicosky KJ , Eimer WA , Tucker S , Ghofrani J , Lefkowitz A , McColl G , Goldstein LE , Tanzi RE , Moir RD (2016) Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease. Sci Transl Med 8, 340ra72.


Bishop GM , Robinson SR (2002) The amyloid hypothesis: Let sleeping dogmas lie? Neurobiol Aging 23, 1101–1105.


Wozniak M , Mee AP , Itzhaki RF (2009) Herpes simplex virus type 1 DNA is located within Alzheimer’s disease amyloid plaques. J Pathol 217, 131–138.


Itzhaki RF (2018) Corroboration of a major role for herpes simplex virus type 1 in Alzheimer’s disease. Front Aging Neurosci 10, 324.


Tzeng NS , Chung CH , Lin FH , Chiang CP , Yeh C Bin , Huang SY , Lu RB , Chang HA , Kao YC , Yeh HW , Chiang WS , Chou YC , Tsao CH , Wu YF , Chien WC (2018) Anti-herpetic medications and reduced risk of dementia in patients with herpes simplex virus infections—a nationwide, population-based cohort study in Taiwan. Neurotherapeutics 15, 417–429.


Itzhaki RF , Lathe R (2018) Herpes viruses and senile dementia: first population evidence for a causal link. J Alzheimers Dis 64, 363–366.


Readhead B , Haure-Mirande JV , Funk CC , Richards MA , Shannon P , Haroutunian V , Sano M , Liang WS , Beckmann ND , Price ND , Reiman EM , Schadt EE , Ehrlich ME , Gandy S , Dudley JT (2018) Multiscale analysis of independent Alzheimer’s cohorts finds disruption of molecular, genetic, and clinical networks by human herpesvirus. Neuron 99, 64–82.


Lin WR , Wozniak MA , Cooper RJ , Wilcock GK , Itzhaki RF (2002) Herpesviruses in brain and Alzheimer’s disease. J Pathol 197, 395–402.


Venegas C , Kumar S , Franklin BS , Dierkes T , Brinkschulte R , Tejera D , Vieira-Saecker A , Schwartz S , Santarelli F , Kummer MP , Griep A , Gelpi E , Beilharz M , Riedel D , Golenbock DT , Geyer M , Walter J , Latz E , Heneka MT (2017) Microglia-derived ASC specks crossseed amyloid-β in Alzheimer’s disease. Nature 552, 355.


Tejera D , Mercan D , Sanchez-Caro JM , Hanan M , Greenberg D , Soreq H , Latz E , Golenbock D , Heneka MT (2019) Systemic inflammation impairs microglial Aβ clearance through NLRP3 inflammasome. EMBO J 38, e101064.


Keshavan M (2019) On Alzheimer’s, scientists head back to the drawing board — and once-shunned ideas get an audience. STAT News,, Posted 22 July 2019, Accessed 21 August 2019.


DevanandDP. Anti-viral Therapy in Alzheimer’s Disease., Last updated 11 April 2019, Accessed 21 August 2019.


Poole S , Singhrao SK , Chukkapalli S , Rivera M , Velsko I , Kesavalu L , Crean SJ (2015) Active invasion of porphyromonas gingivalis and infection-induced complement activation in apoe-/- mice brains. J Alzheimers Dis 43, 67–80.


Dominy SS , Lynch C , Ermini F , Benedyk M , Marczyk A , Konradi A , Nguyen M , Haditsch U , Raha D , Griffin C , Holsinger LJ , Arastu-Kapur S , Kaba S , Lee A , Ryder MI , Potempa B , Mydel P , Hellvard A , Adamowicz K , Hasturk H , Walker GD , Reynolds EC , Faull RLM , Curtis MA , Dragunow M , Potempa J (2019) Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv 5, eaau3333.


National Institute on Aging (1 April 2019) Notice of Special Interest: High-Priority Research Topic for PAR-19-070. Retrieved from


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Leslie Norins, Ph.D. wrote this fantastic paper:

Alzheimer’s has had a Cabal similarly to Lyme in that research has been hijacked by a group of individuals with blinders on.  According to Norins, the 2017 Alzheimer’s Association had a conference in London where researchers from 70 countries could share progress.  A keyword index of the presentations showed the largest entries, 110, were for amyloid/APP.The next most common item was tau, the tangled protein, with 85 entries. Inflammation—the body’s reaction to something—had 45 mentions.  Presentations of germ importance had only single digit presence: prion proteins (8 entries), infectious disease (4 entries), bacteria (1 entry). Virus was not even listed as a keyword.

Yet numerous researchers have doggedly fought against the myopic focus and have found spirochetes in the brains of Alzheimer’s patients:, and Kris Kristofferson was diagnosed with Alzheimer’s but actually had Lyme disease:  Fantastic read by microbiologist Tom Grier.

I was saddened to read that Robert Moir died recently of glioblastoma, a type of brain cancer.

Lyme has been implicated in glioblastoma:



The Link Between Lyme Disease and Dementia

The Link Between Lyme Disease and Dementia

Lyme disease results from infection with the bacterium Borrelia burgdorferi, which is transmitted to humans through the bite of some ticks. Common early symptoms of the illness include fever, headache, fatigue and a characteristic red rash (erythema migrans) at the site of the tick bite.

Early diagnosis is crucial. The sooner Lyme disease is recognised, the easier it is to cure fully with a course of oral antibiotics. As the infection progresses, it may become a lot more persistent. If left untreated for a long time, Lyme disease may enter a chronic phase. The infection can spread throughout the body and cause serious joint, heart and neurological symptoms.

Since the erythema migrans rash is absent in 20–30% of patients and the other symptoms can mimic other illnesses, Lyme disease is often difficult to diagnose. The available laboratory tests are also unreliable in the early stages of the illness. Therefore, doctors have to consider factors such as the patient’s history of tick bites and recent visits to high-risk areas, in addition to any physical signs and symptoms, when making a diagnosis.

Lyme Disease and the Brain

Some common questions about Lyme disease and the brain are ‘Can Lyme disease cause dementia-like symptoms?’ and ‘Does Lyme disease cause memory problems?’ To answer these, let’s take a look at the stats.

Lyme disease leads to profound effects on the brain in about 15% of cases. Some sources suggest that this proportion may be even higher, since thousands of cases are believed to remain undiagnosed every year. A small percentage of patients continue to experience neurological symptoms after receiving timely antibiotic treatment for Lyme disease. This phenomenon is often referred to as ‘post-treatment Lyme disease syndrome’, and its possible cause is a widespread inflammation of the brain.

Neurological Symptoms of Lyme Disease

Chronic Lyme disease develops when the infection remains unrecognised and untreated for a long time. In patients with strong immune systems, the initial symptoms can be very mild and may even go unnoticed. The bacteria can live inside the cells and not cause any problems for several months or even years.

Serious symptoms of chronic Lyme disease tend to first appear when immune function becomes disrupted due to another illness, stress or environmental factors. This is when the bacteria begin to proliferate at a greater pace, and travel to various different tissues and organs.

When Lyme disease becomes chronic and the bacteria spread to the brain, the resulting condition is referred to as neuroborreliosis. Common neurological and psychological symptoms of neuroborreliosis are cognitive decline, memory impairment, mood swings, decreased energy levels, difficulty concentrating, sleep disturbances, disrupted fine motor control and vision changes.

In rare cases, neuropsychiatric Lyme disease can cause paranoia, hallucinations, mania and obsessive-compulsive symptoms. In children, the most common symptoms of neuroborreliosis are headaches, behavioral changes, learning difficulties and sleep disorders.

Patients with chronic Lyme disease often report extreme fatigue. They can sleep for as many as 10 to 12 hours, yet not feel rested after waking up. Increased sensitivity to light and loud sounds can also develop.

Diagnosing Neurological Lyme Disease

In addition to serological testing, patients with suspected neuroborreliosis may benefit from a brain MRI scan. The scan may reveal lesions similar to those caused by multiple sclerosis. Spine lesions have also been observed in some cases. Other diagnostic methods to consider are nerve conduction studies and neurocognitive tests.

Secondary Dementia Due to Lyme Neuroborreliosis

Severe dementia resulting from neuroborreliosis is extremely rare. However, dementia-like syndromes associated with Lyme disease have been reported on occasion.

In a few cases, the condition has seemed to trigger primary dementia, such as Alzheimer’s disease. Persistent chronic Lyme disease is normally treated with several courses of intravenous antibiotics, but it’s unclear whether serious neuropsychiatric symptoms are completely reversible.

Lyme Disease and Dementia/Alzheimer’s Disease

The dementia and other signs of cognitive decline caused by severe neuroborreliosis tend to resemble the symptoms of Alzheimer’s disease. Some research studies have indicated the presence of Borrelia burgdorferi in the brains of Alzheimer’s patients, suggesting a possible link between the two conditions. While Lyme disease can be successfully cured with antibiotics in most cases, the exact causes of Alzheimer’s disease remain unknown, and no effective treatment currently exists.

So how does Lyme affect you in old age? Well, one 2014 study aimed to determine if there was an actual relationship between Lyme and Alzheimer’s. The scientists collected data from the US Centers for Disease Control and Prevention on the incidence of Lyme disease and deaths associated with Alzheimer’s disease. They then analysed the information in search of any significant correlations.

One of the findings of the study was that the 13 states with the highest prevalence of Lyme disease actually had the lowest number of deaths from Alzheimer’s disease. Moreover, the seven states with the highest incidence rates of Alzheimer’s were among the 13 states with the fewest number of Lyme disease cases. Vermont was the only state reporting a high incidence of both conditions. Any other potential associations were found to be statistically insignificant.

The link between Lyme disease and dementia remains unclear, but considering the other possible implications of contracting chronic Lyme, it’s better to be safe than sorry and protect yourself against tick bites altogether.


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Inflammatory Processes Drive Progression of Alzheimer’s and Other Brain Diseases

Inflammatory processes drive progression of Alzheimer’s and other brain diseases

Summary: The NLPR3 inflammasome and the inflammatory response it triggers play a critical role in the emergence of tau pathology.Source: DZNE

Inflammation drives the progression of neurodegenerative brain diseases and plays a major role in the accumulation of tau proteins within neurons. An international research team led by the German Center for Neurodegenerative Diseases (DZNE) and the University of Bonn comes to this conclusion in the journal Nature. The findings are based on the analyses of human brain tissue and further lab studies. In the particular case of Alzheimer’s the results reveal a hitherto unknown connection between Amyloid Beta and tau pathology. Furthermore, the results indicate that inflammatory processes represent a potential target for future therapies.

Tau proteins usually stabilize a neuron’s skeleton. However, in Alzheimer’s disease, frontotemporal dementia (FTD), and other “tauopathies” these proteins are chemically altered, they detach from the cytoskeleton and stick together. As a consequence, the cell’s mechanical stability is compromised to such an extent that it dies off. In essence, “tau pathology” gives neurons the deathblow. The current study led by Prof. Michael Heneka, director of the Department of Neurodegenerative Diseases and Gerontopsychiatry at the University of Bonn and a senior researcher at the DZNE, provides new insights into why tau proteins are transformed. As it turns out, inflammatory processes triggered by the brain’s immune system are a driving force.

A Molecular Switch

A particular protein complex, the “NLRP3 inflammasome”, plays a central role for these processes, the researchers report in Nature. Heneka and colleagues already studied this macromolecule, which is located inside the brain’s immune cells, in previous studies. It is a molecular switch that can trigger the release of inflammatory substances. For the current study, the researchers examined tissue samples from the brains of deceased FTD patients, cultured brain cells, and mice that exhibited hallmarks of Alzheimer’s and FTD.

“Our results indicate that the inflammasome and the inflammatory reactions it triggers, play an important role in the emergence of tau pathology”, Heneka said. In particular, the researchers discovered that the inflammasome influences enzymes that induce a “hyperphosphorylation” of tau proteins. This chemical change ultimately causes them to separate from the scaffold of neurons and clump together. “It appears that inflammatory processes mediated by the inflammasome are of central importance for most, if not all, neurodegenerative diseases with tau pathology.”

A Link between Amyloid Beta and Tau

This especially applies to Alzheimer’s disease. Here another molecule comes into play: “amyloid beta” (Amyloid Beta). In Alzheimer’s, this protein also accumulates in the brain. In contrast to tau proteins, this does not happen within the neurons but between them. In addition, deposition of Amyloid Beta starts in early phases of the disease, while aggregation of tau proteins occurs later.

This shows a head with a swirly background

In previous studies, Heneka and colleagues were able to show that the inflammasome can promote the aggregation of Amyloid Beta. Here is where the connection to the recent findings comes in. “Our results support the amyloid cascade hypothesis for the development of Alzheimer’s. According to this hypothesis, deposits of Amyloid Beta ultimately lead to the development of tau pathology and thus to cell death,” said Heneka. “Our current study shows that the inflammasome is the decisive and hitherto missing link in this chain of events, because it bridges the development from Amyloid Beta pathology to tau pathology. It passes the baton, so to speak.” Thus, deposits of Amyloid Beta activate the inflammasome. As a result, formation of further deposits of Amyloid Beta is promoted. On the other hand, chemical changes occur to the tau proteins resulting into their aggregation.

A Possible Starting Point for Therapies

“Inflammatory processes promote the development of Amyloid Beta pathology, and as we have now been able to show, of tau pathology as well. Thus, the inflammasome plays a key role in Alzheimer’s and other brain diseases,” said Heneka, who is involved in the Bonn-based “ImmunoSensation” cluster of excellence and who also teaches at the University of Massachusetts Medical School. With these findings, the neuroscientist sees opportunities for new treatment methods. “The idea of influencing tau pathology is obvious. Future drugs could tackle exactly this aspect by modulating the immune response. With the development of tau pathology, mental abilities decline more and more. Therefore, if tau pathology could be contained, this would be an important step towards a better therapy.”


Media Contacts:
Marcus Neitzert – DZNE
Image Source:
The image is in the public domain.

Original Research: Closed access
“NLRP3 inflammasome activation drives tau pathology”. Christina Ising et al.
Nature doi:10.1038/s41586-019-1769-z.


NLRP3 inflammasome activation drives tau pathology

Alzheimer’s disease is characterized by the accumulation of amyloid-beta in plaques, aggregation of hyperphosphorylated tau in neurofibrillary tangles and neuroinflammation, together resulting in neurodegeneration and cognitive decline1. The NLRP3 inflammasome assembles inside of microglia on activation, leading to increased cleavage and activity of caspase-1 and downstream interleukin-1β release2. Although the NLRP3 inflammasome has been shown to be essential for the development and progression of amyloid-beta pathology in mice3, the precise effect on tau pathology remains unknown. Here we show that loss of NLRP3 inflammasome function reduced tau hyperphosphorylation and aggregation by regulating tau kinases and phosphatases. Tau activated the NLRP3 inflammasome and intracerebral injection of fibrillar amyloid-beta-containing brain homogenates induced tau pathology in an NLRP3-dependent manner. These data identify an important role of microglia and NLRP3 inflammasome activation in the pathogenesis of tauopathies and support the amyloid-cascade hypothesis in Alzheimer’s disease, demonstrating that neurofibrillary tangles develop downstream of amyloid-beta-induced microglial activation.


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Finding Link Between Infection & Alzheimer’s Disease Could Be Worth $ 1 Million–Public-Health/Article/10-19/Finding-Link-Between-Infection-and-Alzheimer-s-Disease-Could-Be-Worth-1-Million/56312  Full article here

Finding Link Between Infection and Alzheimer’s Disease Could Be Worth $1 Million

OCTOBER 15, 2019

By Tom Rosenthal

WASHINGTON—If you can present persuasive evidence that a particular microbe causes Alzheimer’s disease, there’s a $1 million prize waiting for you.

“This is an award for achievement; it is not a grant,” said Leslie N. Norins, MD, PhD, FIDSA, the founder and CEO of Alzheimer’s Germ Quest, Inc. ( The nonprofit group is funding the award to encourage more intensive research on the possibility that microorganisms are the root cause of the incurable disease afflicting 47 million people worldwide, including 5.6 million Americans aged 65 years and older.

“I’ve closely reviewed the scientific literature and personally believe it’s clear that one germ, possibly not yet discovered, is the root cause of most Alzheimer’s disease,” Dr. Norins said. “But we’ll see what researchers find out.”



I posted on this a year ago when Leslie Norins, Ph.D. wrote this fantastic paper:

Alzheimer’s has had a Cabal similarly to Lyme in that research has been hijacked by a group of individuals with blinders on.  According to Norins, the 2017 Alzheimer’s Association had a conference in London where researchers from 70 countries could share progress.  A keyword index of the presentations showed the largest entries, 110, were for amyloid/APP.The next most common item was tau, the tangled protein, with 85 entries. Inflammation—the body’s reaction to something—had 45 mentions.  Presentations of germ importance had only single digit presence: prion proteins (8 entries), infectious disease (4 entries), bacteria (1 entry). Virus was not even listed as a keyword.

Yet numerous researchers have doggedly fought against the myopic focus and have found spirochetes in the brains of Alzheimer’s patients:, and Kris Kristofferson was diagnosed with Alzheimer’s but actually had Lyme disease:  Fantastic read by microbiologist Tom Grier.

New Alzheimer’s Blood Test 94% Accurate

New Alzheimer’s Blood Test 94% Accurate

Megan Brooks

August 02, 2019

A new blood test to detect brain changes emblematic of early Alzheimer’s disease (AD) has moved one step closer to reality and could be a “game changer” for the field.

Researchers found that measuring the ratio of β-amyloid (Aβ) 42 and Aβ40 in blood using a high-precision assay is 94% accurate in diagnosing brain amyloidosis, using amyloid PET or CSF phosphorylated (p-tau) 181/Aβ42 as reference standards.

“Right now we screen people for clinical trials with brain scans, which is time-consuming and expensive, and enrolling participants takes years,” senior investigator Randall J. Bateman, MD, professor of neurology, Washington University School of Medicine in St. Louis, said in a statement.

“But with a blood test, we could potentially screen thousands of people a month. That means we can more efficiently enroll participants in clinical trials, which will help us find treatments faster, and could have an enormous impact on the cost of the disease as well as the human suffering that goes with it,” he added.

The study was published online August 1 in Neurology.

Easy Screening Tool

Using an immunoprecipitation and liquid chromatography–mass spectrometry assay, the researchers measured Aβ42/Aβ40 in plasma and CSF samples from 158 older, mostly cognitively normal individuals (94% with Clinical Dementia Rate [CDR] = 0) that were collected within 18 months of an amyloid PET scan.

Plasma Aβ42/Aβ40 correlated highly with amyloid PET status (receiver operating characteristic area under the curve [AUC], 0.88; 95% confidence interval [CI], 0.82 – 0.93) and CSF p-tau181/Aβ42 (AUC, 0.85; 95% CI, 0.79 – 0.92), the researchers report.

The combination of plasma Aβ42/Aβ40, age, and apolipoprotein (APOE) ε4 status had “very high” correlation with amyloid PET (AUC, 0.94; 95% CI, 0.90 – 0.97), “suggesting that plasma Aβ42/Aβ40 may be used as a screening tool for those at risk of AD dementia,” the researchers write.

In addition, individuals with a positive plasma Aβ42/Aβ40 but negative amyloid PET scan have a 15-fold higher risk of converting to amyloid PET-positive (P = .01).

“The sensitivity of the plasma Aβ42/Aβ40 assay to amyloid PET-negative individuals who convert to amyloid PET-positive suggests that plasma Aβ42/Aβ40 becomes positive earlier than the established amyloid PET threshold used for this study,” Bateman and colleagues note in their report.

“Therefore, a positive plasma Aβ42/Aβ40 with a negative amyloid PET scan may represent early amyloidosis rather than a false-positive result in some individuals,” they add.

As reported by Medscape Medical News, the study builds on earlier work by the same researchers.


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