Targeting Infectious Agents as a Therapeutic Strategy in Alzheimer's Disease.

Abstract:

:Alzheimer's disease (AD) is the most prevalent dementia in the world. Its cause(s) are presently largely unknown. The most common explanation for AD, now, is the amyloid cascade hypothesis, which states that the cause of AD is senile plaque formation by the amyloid β peptide, and the formation of neurofibrillary tangles by hyperphosphorylated tau. A second, burgeoning theory by which to explain AD is based on the infection hypothesis. Much experimental and epidemiological data support the involvement of infections in the development of dementia. According to this mechanism, the infection either directly or via microbial virulence factors precedes the formation of amyloid β plaques. The amyloid β peptide, possessing antimicrobial properties, may be beneficial at an early stage of AD, but becomes detrimental with the progression of the disease, concomitantly with alterations to the innate immune system at both the peripheral and central levels. Infection results in neuroinflammation, leading to, and sustained by, systemic inflammation, causing eventual neurodegeneration, and the senescence of the immune cells. The sources of AD-involved microbes are various body microbiome communities from the gut, mouth, nose, and skin. The infection hypothesis of AD opens a vista to new therapeutic approaches, either by treating the infection itself or modulating the immune system, its senescence, or the body's metabolism, either separately, in parallel, or in a multi-step way.

journal_name

CNS Drugs

journal_title

CNS drugs

authors

Fülöp T,Munawara U,Larbi A,Desroches M,Rodrigues S,Catanzaro M,Guidolin A,Khalil A,Bernier F,Barron AE,Hirokawa K,Beauregard PB,Dumoulin D,Bellenger JP,Witkowski JM,Frost E

doi

10.1007/s40263-020-00737-1

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

673-695

issue

7

eissn

1172-7047

issn

1179-1934

pii

10.1007/s40263-020-00737-1

journal_volume

34

pub_type

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