The following is a summary of “Proteomic indicators of health predict Alzheimer’s disease biomarker levels and dementia risk,” published in the October 2023 issue of Neurology by Dark et al.
Researchers started a retrospective study to examine the association of 14 protein-based health indicators with plasma and neuroimaging biomarkers of Alzheimer’s disease (AD) and neurodegeneration.
They examined whether 14 protein-based health indices (SomaSignal Tests [SSTs]) were associated with concurrently measured plasma-based biomarkers of AD pathology (Aβ42/40, pTau-181), neuronal injury (neurofilament light chain [NfL]), and reactive astrogliosis (glial fibrillary acidic protein [GFAP]), as well as brain volume and cortical Aβ and tau in 706 cognitively normal adults. Protein-based health indicators associated with neurodegeneration predicted 25-year dementia risk in a separate cohort of 11,285 individuals.
The results showed that lower Aβ42/40 and higher pTau-181, NfL, and GFAP levels were associated with a greater protein-based risk for cardiovascular disease, heart failure mortality, and kidney disease, even in individuals without cardiovascular or kidney disease. Proteomic indicators like body fat percentage, lean body mass, and visceral fat were linked to pTau-181, NfL, and GFAP while resting energy rate was negatively associated with NfL and GFAP. These health indicators collectively predicted 12%, 31%, 50%, and 33% of plasma Aβ42/40, pTau-181, NfL, and GFAP levels. Protein-based cardiovascular risk markers were linked to decreased regional brain volumes and predicted dementia risk over 25 years, even in those without clinically defined cardiovascular disease.
Investigators concluded that subclinical peripheral and cardiovascular health may influence AD and neurodegenerative disease processes and biomarker levels.