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Clinical Manifestations.

Anat Yaskolka Meir1, Ana W Capuano2, Xingyan Wang1

  • 1Harvard T.H. Chan School of Public Health, boston, MA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

This study reveals that muscle peptides correlate with Alzheimer's disease (AD) pathology, while serum peptides are linked to insulin resistance in AD. These findings suggest potential peripheral biomarkers for AD.

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Area of Science:

  • Neuroscience
  • Metabolomics
  • Gerontology

Background:

  • Alzheimer's disease (AD) is linked to protein expression changes in the brain.
  • The relationship between AD dementia and diabetes mellitus (DM) is known, but cross-tissue proteomic associations with AD and DM remain underexplored.

Purpose of the Study:

  • To investigate central-peripheral proteome associations in older adults with and without Alzheimer's disease (AD) and diabetes mellitus (DM).
  • To identify potential peripheral biomarkers for AD pathology and insulin resistance (IR).

Main Methods:

  • Utilized data from the Rush Memory and Aging Project (MAP).
  • Performed TMT-based phosphoproteome profiling on postmortem human brain prefrontal cortex, deltoid muscle, and antemortem serum samples.
  • Matched participants by DM status and determined AD status using NIA-AA pathology criteria.

Main Results:

  • Significant overlap was observed in phosphorylated and unphosphorylated peptides between brain and muscle tissues, and between brain and serum.
  • Muscle phosphorylated peptides correlated with AD-related brain peptides and were enriched in pathways like muscle contraction and neurodegenerative diseases.
  • Serum phosphorylated peptides were enriched in insulin resistance (IR) pathways, suggesting a link to IR in AD.

Conclusions:

  • Muscle peptides are predominantly associated with pathological AD, whereas serum peptides are more linked to IR in AD.
  • The study highlights the potential of cross-tissue peptide analysis for discovering peripheral AD biomarkers.
  • Interactions between central and peripheral peptide expression may offer novel insights into AD pathogenesis.