Aβ, tau, α-synuclein, huntingtin, TDP-43, PrP and AA are members of the innate immune system: a unifying hypothesis on the etiology of AD, PD, HD, ALS, CJD and RSA as innate immunity disorders

Bandea, Claudiu I.

doi:10.1101/000604

Cited by 12 publications

(11 citation statements)

References 101 publications

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“…These results are in line with the view that Aβ and tau, together with other proteins involved in neurodegeneration, play a role in the CNS innate immune response [ 42 , 43 ]. In particular, Aβ antimicrobial properties against different pathogens, including HSV-1, have recently been reported [ 44 – 47 ].…”

Section: Discussionsupporting

confidence: 90%

Recurrent herpes simplex virus-1 infection induces hallmarks of neurodegeneration and cognitive deficits in mice

et al. 2019

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Herpes simplex virus type 1 (HSV-1) is a DNA neurotropic virus, usually establishing latent infections in the trigeminal ganglia followed by periodic reactivations. Although numerous findings suggested potential links between HSV-1 and Alzheimer’s disease (AD), a causal relation has not been demonstrated yet. Hence, we set up a model of recurrent HSV-1 infection in mice undergoing repeated cycles of viral reactivation. By virological and molecular analyses we found: i) HSV-1 spreading and replication in different brain regions after thermal stress-induced virus reactivations; ii) accumulation of AD hallmarks including amyloid-β protein, tau hyperphosphorylation, and neuroinflammation markers (astrogliosis, IL-1β and IL-6). Remarkably, the progressive accumulation of AD molecular biomarkers in neocortex and hippocampus of HSV-1 infected mice, triggered by repeated virus reactivations, correlated with increasing cognitive deficits becoming irreversible after seven cycles of reactivation. Collectively, our findings provide evidence that mild and recurrent HSV-1 infections in the central nervous system produce an AD-like phenotype and suggest that they are a risk factor for AD.

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Section: Discussionsupporting

confidence: 90%

Recurrent herpes simplex virus-1 infection induces hallmarks of neurodegeneration and cognitive deficits in mice

et al. 2019

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“…Other data have suggested that this host reaction is a primitive, acellular, innate immune reaction. These data were obtained either via homology [9] or via studies of the effects of virus infection on either mice or cell cultures [10]. If the virusgenerated trigger for the innate immune response has structural features in common among several different viruses, then vaccination against all of these viruses would be an obvious way to reduce the frequency of Alzheimer's disease.…”

Section: Foundation For An Explanation: Basicsmentioning

confidence: 99%

A Protein Assembly Hypothesis for Population-Specific Decrease in Dementia with Time

Serwer

Wright

2021

Biophysica

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A recent report in the journal, Neurology, documents age-normalized, nation-specific (e.g., United States and Western Europe), progressive decrease of dementia, beginning about 25 years ago. This observation has, thus far, not had explanation. We begin our proposed explanation with the following previous disease construct. (1) Some dementia is caused by innate immune over-response to infections. (2) The innate immune over-response occurs via excessive conversion of amyloid protein to α-sheet conformation. (3) This conversion evolved to inhibit invading microbes by binding microbe-associated α-sheet, e.g., in hyper-expanded capsid intermediates of some viruses. The rarity of human α-sheet makes this inhibition specific for microbial invaders. As foundation, here we observe directly, for the first time, extreme, sheet-like outer shell thinness in a hyper-expanded capsid of phage T3. Based on phage/herpesvirus homology, we propose the following. The above decrease in dementia is caused by varicella-zoster virus (VZV) vaccination, USFDA-approved about 25 years ago; VZV is a herpesvirus and causes chickenpox and shingles. In China and Japan, a cotemporaneous non-decrease is explained by lower anti-VZV vaccination. Co-assembly extension of α-sheet is relatively independent of amino acid sequence. Thus, we project that additional dementia is suppressible by vaccination against other viruses, including other herpesviruses.

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“…Finally, evidence exists that not all components of the innate immune system have been investigated as such. For example, evidence exists that amyloid-forming proteins are part of a mostly acellular innate immune system that causes neurodegenerative disease when malfunctioning [ 69 ].…”

Section: A Guideline Based On the Above: Support From Fundamental mentioning

confidence: 99%

Using the Past to Maximize the Success Probability of Future Anti-Viral Vaccines

Serwer¹

2020

Vaccines

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Rapid obtaining of safe, effective, anti-viral vaccines has recently risen to the top of the international agenda. To maximize the success probability of future anti-viral vaccines, the anti-viral vaccines successful in the past are summarized here by virus type and vaccine type. The primary focus is on viruses with both single-stranded RNA genomes and a membrane envelope, given the pandemic past of influenza viruses and coronaviruses. The following conclusion is reached, assuming that success of future strategies is positively correlated with strategies successful in the past. The primary strategy, especially for emerging pandemic viruses, should be development of vaccine antigens that are live-attenuated viruses; the secondary strategy should be development of vaccine antigens that are inactivated virus particles. Support for this conclusion comes from the complexity of immune systems. These conclusions imply the need for a revision in current strategic planning.

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Aβ, tau, α-synuclein, huntingtin, TDP-43, PrP and AA are members of the innate immune system: a unifying hypothesis on the etiology of AD, PD, HD, ALS, CJD and RSA as innate immunity disorders

Abstract: Despite decades of research, thousands of studies and numerous advances,

Cited by 12 publications

References 101 publications

Recurrent herpes simplex virus-1 infection induces hallmarks of neurodegeneration and cognitive deficits in mice

Recurrent herpes simplex virus-1 infection induces hallmarks of neurodegeneration and cognitive deficits in mice

A Protein Assembly Hypothesis for Population-Specific Decrease in Dementia with Time

Using the Past to Maximize the Success Probability of Future Anti-Viral Vaccines

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