Moderating effects of plasma glial fibrillary acidic protein along the Alzheimer's disease continuum

Year: 2025

Type: article

Abstract: INTRODUCTION Glial fibrillary acidic protein (GFAP) may contribute to Alzheimer's pathology at early disease stages. GFAP moderation of Alzheimer's disease (AD)‐related neurodegeneration and cognition is unclear. METHODS We examined plasma GFAP moderation of AD biomarkers (amyloid beta [Aβ]‐positron emission tomography [PET][A]; plasma phosphorylated tau‐181 [p‐tau181][T 1 ]), neurodegeneration (plasma NfL[N plasma ]; structural magnetic resonance imaging [MRI][N MRI ]), and cognition (Cog memory ; Cog executive ) in two cohorts: University of California San Francisco (UCSF) ( N = 212, 91.0% non‐Hispanic/Latino White [NHLW], age = 74.7 [7.6] years, 75.9% cognitively unimpaired [CU]) and 1Florida Alzheimer's Disease Research Centers (1FLADRC; N = 582, 32.8% NHLW, age = 70.7 [8.5] years, 28.9% CU). RESULTS Plasma GFAP consistently moderated A–T 1 (UCSF: β = 0.46, p = 0.012; 1FLADRC: β = 0.12, p = 0.029). The association between elevated Aβ‐PET and increased (p‐tau) was strengthened at higher GFAP concentrations. In 1FLADRC, GFAP moderated T 1 –N plasma/MRI. In UCSF, GFAP moderated T 1 –Cog memory/executive and N MRI –Cog memory/executive . Higher GFAP consistently related to worse neurodegeneration and cognition (main effects). DISCUSSION Across demographically and clinically heterogeneous cohorts, plasma GFAP is a key moderator of AD and may help identify individuals at greatest risk of AD‐related neurodegeneration and cognitive decline. Highlights AD biomarkers were measured in two demographically and clinically distinct cohorts. Plasma GFAP moderated Aβ‐PET to p‐tau associations in both UCSF and 1FLADRC. Cohort‐dependent, GFAP moderated p‐tau to neurodegeneration and cognition associations. All moderations revealed strengthened disease associations with higher plasma GFAP. Plasma GFAP may help identify individuals at greatest risk of AD‐related decline.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz.70626

Institutions: University of Florida Health, University of Florida, University of California, San Francisco, Florida Atlantic University, Mount Sinai Medical Center, University of Miami

Language: English

Topic: Dementia and Cognitive Impairment Research

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,200

Funders: Alzheimer's Association, Larry L. Hillblom Foundation, National Institutes of Health, National Institute on Aging, National Institute of Neurological Disorders and Stroke

Awards: G1015262670, G1048051091, Do Lifestyles Induce Cell Plasticity? A Molecular Query Across Human Trials, Synaptic Proteome in Genetic Frontotemporal Lobar Degeneration, G1253688923, G1632916191, G2663712431, G3467470903, G3603874756, G3842034552, G461021441, G4740807435, G495832400, G6160646532, G6484036209, G6570754590, Novel Imaging and Biofluid Biomarkers of Small Vessel Cerebrovascular Disease, Passive digital phenotyping for early detection of frontotemporal dementia, G816726602, G89556848, G9000007463, G9000032792, G9000049522, G9000060917, G9000079798, G9000109462, Deciphering the molecular landscape of frontotemporal lobar degeneration: A network-based proteomic approach, Validation of Novel Plasma Biomarkers for Mixed Etiology Dementia, Unraveling the intersection of synaptic biology, lifestyle, and cognitive resilience

OpenAlex ID: W4414010708