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Systemic Immune Dyshomeostasis Model and Pathways in Alzheimer’s Disease

Authors
  • Talwar, Puneet1
  • Kushwaha, Suman1
  • Gupta, Renu2
  • Agarwal, Rachna3
  • 1 Department of Neurology, Institute of Human Behaviour and Allied Sciences (IHBAS), University of Delhi, Delhi , (India)
  • 2 Department of Microbiology, Institute of Human Behaviour and Allied Sciences (IHBAS), University of Delhi, Delhi , (India)
  • 3 Department of Neurochemistry, Institute of Human Behaviour and Allied Sciences (IHBAS), University of Delhi, Delhi , (India)
Type
Published Article
Journal
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Publication Date
Oct 23, 2019
Volume
11
Identifiers
DOI: 10.3389/fnagi.2019.00290
Source
Frontiers
Keywords
Disciplines
  • Neuroscience
  • Mini Review
License
Green

Abstract

Alzheimer’s disease (AD) still remains an enigma for researchers and clinicians. The onset of AD is insidious, gradually progressive and multifactorial. The recent accumulated scientific evidences suggests that the pathological changes resemble the autoimmune-driven self-sustaining inflammatory process as a result of prolonged oxidative stress and immune dyshomeostasis. Apart from aging, during life span various other factors—mainly environmental, lifestyle, chronic stress, polymicrobial infections and neuroendocrine functions—affect the immune system. Here, we provide crosstalk among “trigger insults/inflammatory stimulus” i.e., polymicrobial infection, chronic stress, pro-inflammatory diet and cholinergic signaling to put forward a “Systemic Immune Dyshomeostasis” model as to connect the events leading to AD development and progression. Our model implicates altered cholinergic signaling and suggests pathological stages with various modifiable risk factors and triggers at different chronological age and stage of cognitive decline. The search of specific autoantibodies for AD which may serve as the suitable blood/CSF biomarkers should be actively pursued for the early diagnosis of AD. The preventive and therapeutic strategies should be directed towards maintaining the normal functioning of the immune system throughout the life span and specific modulation of the immune responses in the brain depending on the stage of changes in brain.

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