Abstract
Alzheimers Dement. 2024 Dec;20 Suppl 1:e092720. doi: 10.1002/alz.092720.
ABSTRACT
BACKGROUND: Vascular cognitive impairment/dementia (VD) is the second most prevalent cause of dementia following Alzheimer's disease (AD). VD is characterized by the progression of white matter hyperintensity burden (WMH) and associated neurodegeneration. GFAP, a biomarker for reactive astrogliosis, is associated with Aβ pathology and mediates tau-pathology in preclinical AD. However, the association of GFAP levels with the markers associated with VD is poorly understood.
METHOD: We assessed 796 participants from a research cohort (TRIAD: 355) and a memory clinic cohort (BICWALZ: 441) that were divided into four groups according to their Aβ (Aβ+/Aβ-) and WMH status (WMH+/WMH-). WMH values were corrected by intracranial volume, and cutoffs were determined based on the highest WMH value within 50% of the individuals with the lowest WMH rate in the CU Aβ- group. Biomarker mean level differences between groups were estimated via Ancova Tukey's test, and linear regressions accounting for age, sex, and cognitive status were used to estimate the association.
RESULT: For TRIAD, WMH+/Aβ+ individuals exhibit higher levels of plasma GFAP when compared to all groups except WMH-/Aβ+, with no differences in NfL levels and hippocampal volume between groups (Fig. 1A). In BICWALZ, only hippocampal volume differs between groups with lower levels observed in both WMH-/Aβ- and WMH-/Aβ+ (Fig. 1B''). The association of GFAP and NfL was observed in all groups (Fig. 2A, 2B'). On the other hand, hippocampal degeneration was associated with higher GFAP levels in individuals with abnormal WMH and absence of Aβ burden in both cohorts (Fig. 3A: TRIAD: β = -0.3036; p = 0.0195; Fig. 3B': BICWALZ: β = -0.1791; p = 0.0125).
CONCLUSION: Our findings suggest that astrocyte reactivity, as indicated by plasma GFAP levels, plays a significant role in the hippocampal atrophy observed in patients with vascular disease. These results suggest that therapies targeting astrocyte reactivity could potentially alleviate progressive cognitive deficits commonly found in patients with chronic vasculopathy.
PMID:39751254 | DOI:10.1002/alz.092720
UK DRI Authors
