Plasma GFAP for populational enrichment of clinical trials in preclinical Alzheimer's disease.

Alzheimer's & dementia : the journal of the Alzheimer's Association 2025

["Bellaver Bruna", "Povala Guilherme", "Ferreira Pamela C L", "Bauer-Negrini Guilherme", "Lussier Firoza Z"]

Abstract

Cognitively unimpaired (CU) amyloid beta (Aβ)+ individuals with elevated plasma glial fibrillary acidic protein (GFAP) have an increased risk of Alzheimer’s disease (AD)-related progression. We tested the utility of plasma GFAP for population enrichment CU populations in clinical trials. We estimated longitudinal progression, effect size, and costs of hypothetical clinical trials designed to test an estimated 25% drug effect on reducing tau positron emission tomography (PET) accumulation in the medial temporal lobe (MTL) and temporal neocortical region (NEO-T). CU GFAP+/Aβ+ individuals present an increased annual rate of change and effect size in tau PETMTL and tau PETNEO-T compared to the other groups. An enrichment strategy selecting CU GFAP+/Aβ+ individuals would require a smaller sample size (≈ 57% reduction) and fewer Aβ PET scans (≈ 74% reduction) than trials enriched with Aβ PET alone, reducing total clinical trial costs by up to 64%. Our results suggest that clinical trials focusing on preclinical AD recruiting Aβ+ individuals with elevated GFAP levels would improve cost effectiveness. Cognitively unimpaired (CU) glial fibrillary acidic protein (GFAP)+/amyloid beta (Aβ)+ shows increased changes in tau positron emission tomography (PET) . CU GFAP+/Aβ+ enriched clinical trials require a reduced sample size compared to Aβ+ only. CU GFAP+/Aβ+ enrichment reduces Aβ PET scans required and costs. CU GFAP+/Aβ+ enrichment allows the selection of individuals at early stages of the Alzheimer’s disease continuum.

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