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

Chatterjee, Pratishtha; Vermunt, Lisa; Gordon, Brian A.; Pedrini, Steve; Boonkamp, Lynn; Armstrong, Nicola J.; Xiong, Chengjie; Singh, Abhay K.; Li, Yan; Sohrabi, Hamid R.; Taddei, Kevin; Molloy, Mark; Benzinger, Tammie L. S.; Morris, John C.; Karch, Celeste; Berman, Sarah; Chhatwal, Jasmeer; Cruchaga, Carlos; Graff-Radford, Neill R.; Day, Gregory S.; Farlow, Martin; Fox, Nick; Goate, Alison; Hassenstab, Jason; Lee, Jae-Hong; Levin, Johannes; McDade, Eric; Mori, Hiroshi; Perrin, Richard; Sanchez-Valle, Raquel; Schofield, Peter R.; Levey, Allan; Jucker, Mathias; Masters, Colin L.; Fagan, Anne M.; Bateman, Randall J.; Martins, Ralph N. und Teunissen, Charlotte (2022): Plasma glial fibrillary acidic protein in autosomal dominant Alzheimer's disease: Associations with A beta-PET, neurodegeneration, and cognition. In: Alzheimer's & Dementia, Bd. 19, Nr. 7: S. 2790-2804

Abstract

BackgroundGlial 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 (A beta) accumulation and prior to neurodegeneration and cognitive decline. Plasma GFAP distinguished A beta-positive from A beta-negative ADAD participants and showed a stronger relationship with A beta 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 A beta-related astrocyte reactivity that is associated with cognitive decline and neurodegeneration. HighlightsPlasma 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1552-5260
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198