When the infectious environment meets the AD brain

Abstract

Background The Amyloid theory of Alzheimer’s disease (AD) suggests that the deposition of Amyloid β (Aβ) in the brain triggers a chain of events, involving the deposition of phosphorylated Tau and other misfolded proteins, leading to neurodegeneration via neuroinflammation, oxidative stress, and neurovascular factors. The infectious theory linked various infectious agents with the development of AD, raising the possibility that they serve as etiological causes of the disease. Are these theories mutually exclusive, or do they coincide? Main body In this review, we will discuss how the two theories converge. We present a model by which (1) the systemic infectious burden accelerates the development of AD brain pathology via bacterial Amyloids and other pathogen-associated molecular patterns (PAMPs), and (2) the developing AD brain pathology increases its susceptibility to the neurotoxicity of infectious agents -derived PAMPs, which drive neurodegeneration via activated microglia. Conclusions The reciprocal effects of amyloid deposition and systemic infectious burden may lead to a vicious cycle fueling Alzheimer’s disease pathogenesis.

Oligodendrocyte progenitor cells differentiation induction with MAPK/ERK inhibitor fails to support repair processes in the chronically demyelinated CNS

“…The pump cannulas were inserted into the lateral ventricle, at coordinates A = 0, L = 1. H = 2.5, as previously described (Ganz, Fainstein, & Ben‐Hur, 2022). Pump placement and fixation were performed according to the manufacturer's instructions.…”

Cardiovascular health, infection burden, and incident dementia in the UK Biobank

“…Fourth, and more consequential, infections likely play a causal role in AD pathogenesis 29 . A hypothetical model suggests that systemic and bacterial amyloids and other PAMPs accelerate brain pathology in AD, 2 in which the mutual effects of amyloid accumulation and systemic infection lead to increasing AD pathology 2 . Although Aβ alone is unlikely sufficient to trigger neurodegeneration, its neurotoxicity is asserted by PAMP presence 2 .…”

“…Although dementia is among the leading causes of disability and death in older adults, especially in developed countries, its etiology remains elusive and appears to be multifactorial in nature 1–3 . There is growing evidence that exposure to viral and bacterial infections, such as herpesviruses, gastrointestinal microorganisms, oral bacterial species, Chlamydia pneumonia , and spirochetes, may be associated with dementia due to Alzheimer's disease (AD) 1 .…”

“…Whereas pathophysiological mechanisms linking these infectious agents to AD‐related dementia necessitate further elucidation, it is hypothesized that host immune response to these infectious agents may trigger or accelerate AD processes, which include the accumulation of amyloid beta (Aβ), pathogenic tau protein, and neuroinflammation 1 . Infectious agents and their associated molecules may penetrate leaky blood‐brain barriers and accelerate Aβ deposition, thereby inducing neurotoxic activation of microglia and leading to a vicious cycle of neurodegeneration induced by pathogen‐associated molecular patterns (PAMPs), especially in brain areas with AD pathology 2 …”

Rationale for a Multi-Factorial Approach for the Reversal of Cognitive Decline in Alzheimer’s Disease and MCI: A Review

“…Additionally, while mold exposure has historically been connected with asthma and lung disease, mold-exposed people have reported impaired memory and concentration [ 197 , 241 , 242 , 243 ]. Mold toxins, including trichothecenes from Stachybotrys , aflatoxin from Aspergillus , and ochratoxin A from Aspergillus and Penicillium , are risk factors for the progression of AD because of their neurotoxic effects and ability to impair cognitive functioning [ 197 , 230 , 241 , 242 , 243 , 244 ]. Researchers are beginning to outline the specific inflammatory pathways by which mold affects the brain, particularly in relation to type 3 (toxic) AD [ 197 ].…”