Plasma glial fibrillary acidic protein in autosomal dominant Alzheimer's disease: Associations with Aβ‐PET, neurodegeneration, and cognition

• DOI: 10.1002/alz.12879
• Publication Date: 2022-12-28T07:58:34Z
• Authors: Pratishtha Chatte...; Lisa Vermunt; Brian A. Gordon; Steve Pedrini; Lynn Boonkamp; Nicola J. Armstrong; Chengjie Xiong; Abhay K. Singh; Yan Li; Hamid R. Sohrabi; Kevin Taddei; Mark Molloy; Tammie L. S. Benz...; John C. Morris; Celeste Karch; Sarah Berman; Jasmeer Chhatwal; Carlos Cruchaga; Neill R. Graff‐Ra...; Gregory S Day; Martin Farlow; Nick Fox; Alison Goate; Jason Hassenstab; Jae‐Hong Lee; Johannes Levin; Eric McDade; Hiroshi Mori; Richard Perrin; Raquel Sanchez‐Valle; Peter R. Schofield; Allan Levey; Mathias Jucker; Colin L. Masters; Anne M. Fagan; Randall J. Bateman; Ralph N. Martins; Charlotte Teunissen
• Keywords: cognition; Plasma glial fibrillary acidic protein; Medical Sciences; Amyloid beta-Peptides; neurodegeneration; Neurosciences; 610; Diseases; tau Proteins; Alzheimer's disease; autosomal dominant Alzheimer's disease; Plasma; 03 medical and health sciences; Cognition; 0302 clinical medicine; Alzheimer Disease; Positron-Emission Tomography; Glial Fibrillary Acidic Protein; Medicine and Health Sciences; Humans; ddc:610; Biomarkers

AbstractBackgroundGlial fibrillary acidic protein (GFAP) is a promising candidate blood‐based biomarker for Alzheimer's disease (AD) diagnosis and prognostication. The timing of its disease‐associated changes, its clinical correlates, and biofluid‐type dependency will influence its clinical utility.MethodsWe evaluated plasma, serum, and cerebrospinal fluid (CSF) GFAP in families with autosomal dominant AD (ADAD), leveraging the predictable age at symptom onset to determine changes by stage of disease.ResultsPlasma GFAP elevations appear a decade before expected symptom onset, after amyloid beta (Aβ) accumulation and prior to neurodegeneration and cognitive decline. Plasma GFAP distinguished Aβ‐positive from Aβ‐negative ADAD participants and showed a stronger relationship with Aβ load in asymptomatic than symptomatic ADAD. Higher plasma GFAP was associated with the degree and rate of neurodegeneration and cognitive impairment. Serum GFAP showed similar relationships, but these were less pronounced for CSF GFAP.ConclusionOur findings support a role for plasma GFAP as a clinical biomarker of Aβ‐related astrocyte reactivity that is associated with cognitive decline and neurodegeneration.Highlights Plasma glial fibrillary acidic protein (GFAP) elevations appear a decade before expected symptom onset in autosomal dominant Alzheimer's disease (ADAD). Plasma GFAP was associated to amyloid positivity in asymptomatic ADAD. Plasma GFAP increased with clinical severity and predicted disease progression. Plasma and serum GFAP carried similar information in ADAD, while cerebrospinal fluid GFAP did not.