Association of plasma GFAP with elevated brain amyloid is dependent on severity of white matter lesions in an Asian cognitively impaired cohort

Joyce R Chong; Yuek Ling Chai; Amelia T Y Yam; Saima Hilal; Henri Vrooman; Narayanaswamy Venketasubramanian; Kaj Blennow; Henrik Zetterberg; Nicholas J Ashton; Christopher P Chen; Mitchell K P Lai

doi:10.1002/dad2.12576

Association of plasma GFAP with elevated brain amyloid is dependent on severity of white matter lesions in an Asian cognitively impaired cohort

Alzheimers Dement (Amst). 2024 Apr 11;16(2):e12576. doi: 10.1002/dad2.12576. eCollection 2024 Apr-Jun.

Authors

Joyce R Chong^{1

2}, Yuek Ling Chai^{1

2}, Amelia T Y Yam^{1

2}, Saima Hilal^{1

2

3

4}, Henri Vrooman⁴, Narayanaswamy Venketasubramanian⁵, Kaj Blennow⁶, Henrik Zetterberg^{6

7}, Nicholas J Ashton⁶, Christopher P Chen^{1

2}, Mitchell K P Lai^{1

2}

Affiliations

¹ Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Kent Ridge Singapore.
² Memory, Aging and Cognition Centre National University Health Systems Kent Ridge Singapore.
³ Saw Swee Hock School of Public Health National University of Singapore and National University Health System Kent Ridge Singapore.
⁴ Department of Radiology and Nuclear Medicine Erasmus Medical Center Rotterdam the Netherlands.
⁵ Raffles Neuroscience Centre Raffles Hospital Singapore Singapore.
⁶ Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology Sahlgrenska Academy University of Gothenburg Göteborg Sweden.
⁷ Department of Neurodegenerative Disease The UCL Queen Square Institute of Neurology London UK.

Abstract

Introduction: While elevated blood glial fibrillary acidic protein (GFAP) has been associated with brain amyloid pathology, whether this association occurs in populations with high cerebral small vessel disease (CSVD) concomitance remains unclear.

Methods: Using a Singapore-based cohort of cognitively impaired subjects, we assessed associations between plasma GFAP and neuroimaging measures of brain amyloid and CSVD, including white matter hyperintensities (WMH). We also examined the diagnostic performance of plasma GFAP in detecting brain amyloid beta positivity (Aβ+).

Results: When stratified by WMH status, elevated brain amyloid was associated with higher plasma GFAP only in the WMH- group (β = 0.383; P < 0.001). The diagnostic performance of plasma GFAP in identifying Aβ+ was significantly higher in the WMH- group (area under the curve [AUC] = 0.896) than in the WMH+ group (AUC = 0.712, P = 0.008).

Discussion: The biomarker utility of plasma GFAP in detecting brain amyloid pathology is dependent on the severity of concomitant WMH.

Highlight: Glial fibrillary acidic protein (GFAP)'s association with brain amyloid is unclear in populations with high cerebral small vessel disease (CSVD).Plasma GFAP was measured in a cohort with CSVD and brain amyloid.Plasma GFAP was better in detecting amyloid in patients with low CSVD versus high CSVD.Biomarker utility of GFAP in detecting brain amyloid depends on the severity of CSVD.

Keywords: Alzheimer's disease; amyloid pathology; blood biomarkers; cerebral small vessel disease; cognitive impairment; glial fibrillary acidic protein; white matter hyperintensity.