The famous Framingham study has produced a plasma protein risk score for MCI and AD. This is valuable, especially for early developing MCI patients, finding the patients who will benefit best from future AD treatments. IMO, this is a perfect tool for Prof. Masters when starting his next AD drug study, not perhaps with PBT2 but ATH434.

The paper is here: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70066

Alzheimers Dement

. 2025 Mar;21(3):e70066.

doi: 10.1002/alz.70066.

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

Habbiburr Rehman ¹, Ting Fang Alvin Ang ^{2 3}, Qiushan Tao ⁴, Rhoda Au ^{1 2 3 5 6 7}, Lindsay A Farrer ^{1 3 5 6 7 8 9}, Wei Qiao Qiu ^{4 7 10}, Xiaoling Zhang ^{1 6 9}; Alzheimer's Disease Neuroimaging Initiative

Affiliations Expand

• PMID: 40156298

DOI: 10.1002/alz.70066

Abstract

Introduction: It is unclear whether aggregated plasma protein risk scores (PPRSs) could be useful in predicting the risks of mild cognitive impairment (MCI) and Alzheimer's disease (AD).

Methods: The Cox proportional hazard model with the Least Absolute Shrinkage and Selection Operator penalty was used to build the PPRSs for MCI and AD in 1515 Framingham Heart Study Generation 2 with 1128 proteins measured in plasma at exam 5 (cognitively normal [CN] = 1258, MCI = 129, AD = 128).

Results: MCI PPRS had a hazard ratio (HR) of 6.97 [5.34, 9.12], with a discriminating power (C-index = 82.52%). AD PPRS had a HR of 5.74 [4.67, 7.05] (C-index = 88.15%). Both PPRSs were also significantly associated with cognitive changes, brain atrophy, and plasma AD biomarkers. Proteins in the MCI and AD PPRSs were involved in several pathways related to leukocyte, chemotaxis, immunity, inflammation, and cellular migration.

Discussion: This study suggests that PPRSs serve well to predict the risk of developing MCI and AD as well as cognitive changes and AD-related pathogenesis in the brain.

Highlights: PPRSs were developed for the risk of AD and AD preclinical stage, MCI. PPRSs were developed for MCI and AD associated with cognitive changes, loss of brain volume, and increasing level of plasma AD biomarkers. Leukocyte, chemotaxis, immunity, inflammation, and cellular migration enriched in proteins were identified as being involved in MCI and AD PPRSs.