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Basic Science and Pathogenesis.

Dallin Dressman1,2, Edric D Winford1,3, Badri N Vardarajan1,2,4

  • 1Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
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PubMed
Summary
This summary is machine-generated.

Maintaining a higher proportion of naive CD8+ T cells and reducing T cell cytotoxicity may protect against brain atrophy and cognitive decline in Alzheimer's disease (AD). This immune profile is linked to greater cortical thickness in middle-aged adults.

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Area of Science:

  • Immunology
  • Neuroscience
  • Genetics

Background:

  • Immune responses in aging and Alzheimer's disease (AD) vary, influenced by genetics, socioeconomic status, race, and ethnicity.
  • Understanding immune phenotypes linked to biological and cognitive aging can reveal AD risk factors and potential therapeutic targets.

Purpose of the Study:

  • To investigate correlations between immune cell phenotypes and cognitive/brain aging markers in a multi-ethnic cohort.
  • To identify immune processes that may influence Alzheimer's disease risk and progression.

Main Methods:

  • Single-cell RNA and T/B cell receptor sequencing of over 439,000 immune cells from 205 participants (ages 29-81).
  • Plasma proteomics data analyzed from 86 participants.
  • Correlations assessed between immune cell proportions, T cell expansion, gene expression, cognitive scores, and cortical thickness, controlling for demographics.

Main Results:

  • Higher cortical thickness associated with increased naive and mucosal-associated invariant T (MAIT) CD8+ T cells, and decreased effector memory cells.
  • Greater cortical thickness linked to reduced T cell clonal expansion and lower expression of antigen presentation/cytotoxicity genes in T cell subtypes.
  • Higher cognitive scores correlated with reduced expression of cytotoxicity, antigen presentation, and antimicrobial defense genes in gamma-delta T cells.

Conclusions:

  • Higher naive CD8+ T cell proportions and reduced T cell cytotoxicity gene expression correlate with greater cortical thickness in AD-relevant brain regions, independent of age.
  • Therapeutic strategies targeting naive T cell maintenance and T cell cytotoxicity/expansion may offer neuroprotection and cognitive benefits in aging and AD.