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. 2019 Mar;21(1):7-19.
doi: 10.31887/DCNS.2019.21.1/vharoutunian.

Is Alzheimer disease a failure of mobilizing immune defense? Lessons from cognitively fit oldest-old

Pavel Katsel  1 , Vahram Haroutunian  2
Affiliations

Is Alzheimer disease a failure of mobilizing immune defense? Lessons from cognitively fit oldest-old

Pavel Katsel et al. Dialogues Clin Neurosci. 2019 Mar.

Abstract

Multifaceted evidence supports the hypothesis that inflammatory-immune mechanisms contribute to Alzheimer disease (AD) neuropathology and genetic association of several immune specific genes (TREM2, CR1, and CD33) suggests that maladaptive immune responses may be pivotal drivers of AD pathogenesis. We reviewed microglia-related data from postmortem AD studies and examined supporting evidence from AD animal models to answer the following questions: i) What is the temporal sequence of immune activation in AD progression and what is its impact on cognition? ii) Are there discordant, "primed", microglia responses in AD vs successful cognitive aging? iii) Does central nervous system (CNS) repair in aging depend on recruitment of the elements of cellular adaptive immune response such as effector T cells, and can the recruitment of systemic immune cells ameliorate AD neuropathology? iv) How effective are the immune-system-based therapeutic approaches currently employed for the treatment of AD?

Keywords: Alzheimer disease; T cell; gene expression; immune response; inflammation; macrophage; microglia; oldest-old.

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Figures

Figure 1.
Figure 1.. Mesh plot of dramatically upregulated immune response genes in nondemented oldest old (right panel) compared with nondemented young-old (left panel) in different stages of dementia in two aging groups. T scores (Y axis) for each individual gene symbol (X axis) were plotted. T scores - standardized measure of change (extension of fold change algorithm) were derived from contrast analysis. Please note that direction of dementia severity (Z axis) is reversed in the lower panel in order to visualize declining immune response in demented oldest-old. ND, nondemented; MCI, mild cognitive impairment; SD, severe dementia. Figure shows meek increase of inflammatory markers in young-old individuals with dementia severity compare to robust upregulation in the nondemented oldest-old, which is suppressed in the earliest stage of dementia in oldest-old.
See this image and copyright information in PMC

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