Document Type
Journal Article
Publication Title
Alzheimer's & Dementia
Volume
19
Issue
7
First Page
2790
Last Page
2804
PubMed ID
36576155
Publisher
Wiley
School
School of Medical and Health Sciences
RAS ID
54109
Funders
Dominantly Inherited Alzheimer Network / NIA / National Health and Medical Research Council / German Centre for Neurodegenerative Diseases / Japan Agency for Medical Research and Development / Alzheimer's Association Grant / Lions Alzheimer's Foundation / Lion's Club International / Alzheimer Nederland / Stichting Dioraphte / Australian Alzheimer's Research Foundation / Open access publishing facilitated by Macquarie University, as part of the Wiley - Macquarie University agreement via the Council of Australian University Librarians.
Grant Number
NHMRC : APP1129627
Abstract
Background: Glial 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. Methods: We 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. Results: Plasma GFAP elevations appear a decade before expected symptom onset, after amyloid beta (A ) accumulation and prior to neurodegeneration and cognitive decline. Plasma GFAP distinguished A -positive from A -negative ADAD participants and showed a stronger relationship with A 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. Conclusion: Our findings support a role for plasma GFAP as a clinical biomarker of A -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.
DOI
10.1002/alz.12879
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Comments
Chatterjee, P., Vermunt, L., Gordon, B. A., Pedrini, S., Boonkamp, L., Armstrong, N. J., . . . Teunissen, C. (2023). Plasma glial fibrillary acidic protein in autosomal dominant Alzheimer's disease: Associations with Aβ-PET, neurodegeneration, and cognition. Alzheimer's & Dementia, 19(7), 2790-2804. https://doi.org/10.1002/alz.12879