β-Amyloid is an Immunopeptide and Alzheimer’s is an Autoimmune Disease

Title:β-Amyloid is an Immunopeptide and Alzheimer’s is an Autoimmune Disease

Volume: 18 Issue: 11

Author(s): Donald F. Weaver *

Affiliation:

• Krembil Research Institute, University Health Network, University of Toronto, Toronto, ON,Canada

Keywords: Alzheimer's disease, dementia, neuroinflammation, autoimmune, cytokine, antimicrobial peptide, amyloid-beta, immunopeptide.

Abstract:

Background: As new biomolecular targets for Alzheimer’s disease (AD) emerge, there is a tendency to regard these as mutually exclusive and in competition, culminating in declarations that since the “amyloid hypothesis is dead” it needs to be replaced by completely different theories. However, given the well-described role of misfolding peptides, particularly β-amyloid (Aβ), in the pathogenesis of AD, the need for a broad-based conceptualization of AD, coalescing different theories into a single harmonized explanation emerges as a viable alternative. Incorporating protein aggregation mechanisms of AD into a more widely-encompassing immunopathic model of AD could accomplish such a goal-a goal which could be achieved by repositioning the role of Aβ as an immunopeptide.

Conclusion: This review presents the concept that Aβ is an immunopeptide and that AD is an autoimmune disease in which Aβ is a key molecular player. Being a peptide with the capacity to alter immune function, Aβ is an immunopeptide; having both antimicrobial and immunomodulatory activities, Aβ is a host defense peptide; having most of the defining properties of cytokines, Aβ satisfies the broad definition of cytokine-the prototypic immunopeptide subtype. In addition to these immunoactivities, Aβ is also directly and independently cytotoxic to neurons by both necrotic and apoptotic mechanisms. Therefore, following brain exposure to immune-instigating stimuli, the innate immune system is activated, leading to the release of Aβ as an immunopeptide (functioning as a host defense peptide or cytokine), which subsequently inflicts a misdirected attack upon the host neurons-an autoimmune event.

Cite this article as:

Weaver F. Donald *, β-Amyloid is an Immunopeptide and Alzheimer’s is an Autoimmune Disease, Current Alzheimer Research 2021; 18 (11) . https://dx.doi.org/10.2174/1567205018666211202141650