Microbial-generated amyloids and Alzheimer's disease (AD).

James M Hill,Walter J Lukiw

doi:10.3389/fnagi.2015.00009

Abstract

Atypical amyloid generation, folding, aggregation and impaired clearance are characteristic pathological features of human neurodegenerative disorders including Alzheimer's disease (AD). What is generally not appreciated is that a major secretory product of microbes is amyloid, and that the contribution of microbial amyloid to the pathophysiology of the human central nervous system (CNS) is potentially substantial. While earlier findings suggested that these amyloids may serve some immune-evasive strategy, it has recently become evident that humans have a tremendously heavy systemic burden of amyloid which may contribute to the pathology of progressive neurological diseases with an amyloidogenic component. This perspective will highlight some recent inroads made into our understanding of the enigmatic role that microbial amyloids may play in the homeostasis and pathology of the CNS with particular reference to AD wherever possible.

Highlights

Atypical amyloid generation, folding, aggregation and impaired clearance are characteristic pathological features of human neurodegenerative disorders including Alzheimer’s disease (AD)
While earlier findings suggested that these amyloids may serve some immune-evasive strategy, it has recently become evident that humans have a tremendously heavy systemic burden of amyloid which may contribute to the pathology of progressive neurological diseases with an amyloidogenic component
It has very recently been found that (i) LPS is capable of inducing a pathogenic Congo red-sensitive β-pleated sheet conformation in prion amyloids (Saleem et al, 2014); and (ii) the infectious microbial burden is significantly associated with both AD development and the propensity of AD amyloids to be stained by Congo red (Bu et al, 2014)