Work

Interactive effects of APOE ɛ4 status and vascular burden on white matter microstructural integrity in aging with and without neurocognitive decline

Year: 2025

Type: article

Abstract: Background Carrying the Apolipoprotein ( APOE ) ε4 allele lowers age of onset and increases Alzheimer's disease (AD) risk. Neuropathological findings suggest a mixed etiology in many AD patients, and vascular pathology is common. Objective This study tested the interactive effect of APOE status and multiple vascular comorbidities on white matter (WM) microstructure in aging and early AD. Methods 195 participants from the VPH-DARE@IT dataset were stratified in low/high vascular burden based on the Framingham Risk Score (BMI version). Tract-based spatial statistics was used for WM analyses. Results There was a main effect of APOE , with APOE ɛ4 carriers having higher fractional anisotropy (FA) and lower axial diffusivity (AxD), mean diffusivity (MD), and radial diffusivity (RD) than non-carriers. There was a main effect of vascular burden with lower FA and higher AxD, MD, and RD in the high-burden than the low-burden group. A significant interaction between APOE genotype and vascular burden was also found for all diffusion indices. Post-hoc comparisons revealed lower left hemisphere WM integrity when comparing the low risk group (i.e., non-carriers low burden) to intermediate risk groups (i.e., non-carriers high burden or ɛ4 carriers low burden). The contrasts between the two intermediate risk groups showed altered WM integrity bilaterally. Only the non-carriers high burden showed greater alterations in WM integrity when compared with the high risk group (i.e., ɛ4 carriers high burden) mainly in right hemisphere tracts. Conclusions These findings indicate an interactive effect of a risk gene and vascular comorbidities on WM integrity in aging and early AD.

Source: Journal of Alzheimer s Disease

DOI: 10.1177/13872877251320660

Authors: Srijan Konwar, Riccardo Manca, Matteo De Marco, Hilkka Soininen, Annalena Venneri

Institutions: Brunel University of London, University of Parma, University of Eastern Finland

Language: English

Topic: Dementia and Cognitive Impairment Research

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: European Commission, NextGenerationEU