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Plasma protein risk scores for mild cognitive impairment and Alzheimer's disease in the Framingham heart study

Habbiburr Rehman1, Ting Fang Alvin Ang2,3, Qiushan Tao4

  • 1Departments of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|March 29, 2025
PubMed
Abstract

Insights

Plasma protein risk scores (PPRSs) effectively predict mild cognitive impairment (MCI) and Alzheimer's disease (AD) risk. These scores also correlate with cognitive decline, brain changes, and Alzheimer's biomarkers, highlighting their predictive potential.

Area of Science:

  • Neuroscience
  • Biomarkers
  • Proteomics

Background:

  • The predictive utility of aggregated plasma protein risk scores (PPRSs) for mild cognitive impairment (MCI) and Alzheimer's disease (AD) remains uncertain.
  • Investigating novel biomarkers for early detection of neurodegenerative diseases is crucial.

Purpose of the Study:

  • To develop and validate plasma protein risk scores (PPRSs) for predicting the risk of MCI and AD.
  • To assess the association of PPRSs with cognitive changes, brain atrophy, and AD biomarkers.

Main Methods:

  • Utilized the Cox proportional hazard model with Least Absolute Shrinkage and Selection Operator penalty.
  • Developed PPRSs for MCI and AD using plasma protein data from 1515 participants in the Framingham Heart Study Generation 2.
  • Measured 1128 proteins in plasma from cognitively normal, MCI, and AD participants.

Main Results:

  • MCI PPRS demonstrated a hazard ratio (HR) of 6.97 (95% CI: 5.34-9.12) with 82.52% discrimination (C-index).
  • AD PPRS showed a HR of 5.74 (95% CI: 4.67-7.05) with 88.15% discrimination (C-index).
  • Both PPRSs significantly correlated with cognitive changes, brain atrophy, and plasma AD biomarkers.

Conclusions:

  • PPRSs are valuable tools for predicting the risk of developing MCI and AD.
  • PPRSs are associated with key indicators of AD pathogenesis, including cognitive decline and brain changes.
  • Identified protein pathways involved in immunity, inflammation, and cellular migration are implicated in MCI and AD risk.
Keywords:
Alzheimer's diseasebrain volumemild cognitive impairmentplasma protein risk scorep‐tau181

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