Frontiers | Pathogenic microbes, the microbiome, and Alzheimer’s disease (AD) | Frontiers in Aging Neuroscience

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and
the leading cause of cognitive and behavioral impairment in
industrialized societies. The cause of AD is unknown and the major risk
factor for AD is age. About 5% of all AD cases have a genetic or
familial cause however the vast majority of all AD cases (~95%) are of
sporadic origin. Both the familial and the sporadic forms of AD share a
common disease phenotype involving at least eight characteristic
features including (i) evidence of uncontrolled oxidative stress; (ii)
up-regulated pro-inflammatory signaling; (iii) changes in innate-immune
signaling; (iv) the progressive accumulation of lesions including
neurofibrillary tangles (NFT) and amyloid beta (Aβ)-containing senile
plaques (SP); (v) significant synaptic signaling deficits; (vi) neurite
and brain cell atrophy; (vii) progressively altered gene expression
patterns that are different from healthy brain aging; and (viii)
progressive cognitive impairment and dementia in the host. There is
currently no cure or adequate clinical treatment for AD, and it remains
unclear how AD originates and propagates throughout the brain and
central nervous system (CNS). Results from recent genome-wide
association studies (GWAS) indicate that a significant portion of
AD-relevant gene signals are not located within gene coding regions
suggesting the contribution of epigenetic or environmental factors to AD
risk. The potential contribution of pathogenic microbes to aging and AD
Importantly, most of the changes seen in AD, such as inflammation,
brain cell atrophy, immunological aberrations, amyloidogenesis, altered
gene expression and cognitive deficits are also seen as a consequence of
microbial infection (Cho and Blaser, 2012; Yatsunenko et al., 2012; Bhattacharjee and Lukiw, 2013; Foster and McVey Neufeld, 2013; Kim et al., 2013; Heintz and Mair, 2014; Mancuso et al., 2014).
This brief communication will review some recent observations on the
potential contribution of pathogens to neurological dysfunction, with
specific reference to AD wherever possible.

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