Work

Parallel neuroinflammatory pathways to cerebrovascular burden and amyloid beta in Alzheimer's disease

Year: 2026

Type: article

Abstract: INTRODUCTION: Upstream neuroinflammation plays an important role in Alzheimer's disease (AD) but remains poorly understood. We tested whether two distinct neuroinflammatory markers are associated with cerebrovascular burden and amyloid beta (Aβ), and downstream, with plasma phosphorylated tau (p-tau217), medial temporal lobe (MTL) cortical and hippocampal atrophy, and memory deficits. METHODS: = 126). We used structural equation modeling to test whether plasma chitinase-3-like protein 1 (YKL-40) and glial fibrillary acidic protein (GFAP) contribute to distinct pathways. RESULTS: Higher plasma YKL-40 was associated with greater white matter hyperintensity (WMH), whereas higher plasma GFAP was related to increased 18F-florbetapir (FBP) standardized uptake value ratio (SUVR). Higher plasma GFAP, WMH, and FBP SUVR were independently associated with increased p-tau217. Plasma p-tau217 was associated with reduced MTL cortical thickness and hippocampal volume. Reduced hippocampal volume was related to worse memory. DISCUSSION: Future work can further investigate these neuroinflammatory pathways as potential therapeutic targets for AD.

Source: Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring

DOI: 10.1002/dad2.70415