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

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

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

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

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