Familial and late-onset Alzheimer's disease: Autoimmune disorders triggered by viral, microbial and allergen mimics of beta-amyloid and APP mutants ?

Beta-amyloid (Aβ) autoantibodies are common in Alzheimer’s disease. Some may be derived from Herpes simplex and from 68 other phages and viruses expressing proteins that exactly match an immunogenic and fibrillogenic VGGVV Aβ sequence.Many other viral, microbial and allergenic proteins (particularly from dust mites) align with Aβ as do proteins from Borrelia burgdoferi, C.Pneumoniae, H.Pylori or P.Gingivalis or S.Mutans that cause periodontitis and tooth loss which are associated with Alzheimer's disease  C.Neoformans which has been associated with a rare but curable form of the disorder also expresses proteins with homology toAβ . Immune-related proteins are present in amyloid plaques and the complement membrane attack complex in neurones in Alzheimer’s disease brains. Alzheimer’s disease may thus be an autoimmune disorder triggered by pathogenic antigens homologous to Aβ, whose antibodies target and kill Aβ containing neurones, via immune activation and complement-related lysis. This scenario explains many epidemiological observations in Alzheimer’s disease, which is more common in women and Afro-Americans, as is HSV-2 seroprevalence; related to the number of pregnancies (exposure to childhood infections) and less severe in nuns (low exposure to sexually transmitted diseases). Atopy and autoimmune disorders are common in Alzheimer’s disease in accord with allergen homology to Aβ, and anti-inflammatory agents reduce Alzheimer’s disease risk. Cancer-causing viruses (papillomavirus, hepatitis B, Epstein-Barr) and plant viruses from Mediterranean diet components align with the Aβ sequence targeted by catalytic autoantibodies, perhaps explaining the inverse association of diet and cancer with Alzheimer’s disease. As a papillomavirus vaccine already exists, it may have a role to play in Alzheimer’s disease. This scenario is also relevant to familial Alzheimer’s disease. Mutant forms of APP₇₁₇ and the Swedish mutant convert the surrounding peptide to matches with commensal bacteria (E.Coli, E. Faecalis, P.Gingivalis) and to viruses with very high seroprevalence (HHV-6, norovirus, influenza and the common cold). Late-onset and Familial Alzheimer’s disease may both be autoimmune disorders caused by diverse common pathogens and allergens homologous to Aβ or mutant APP fragments. Immunosuppressants, vaccination and pathogen elimination may be of benefit in both conditions.See Alzheimer's disease risk factors

Pubmed: Autoimmunity and Alzheimer's and Herpes

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