APOE4 reduction in vascular-associated fibroblasts decreases cerebral amyloid angiopathy and associated vascular dysfunction

Emerging roles of apolipoprotein E4 in cerebral small vessel disease-related cognitive impairment: mechanistic insights and therapeutic perspectives

Cerebral small vessel disease (CSVD) is a major contributor to cognitive decline and vascular cognitive impairment in the elderly. However, the extent to which apolipoprotein E4 (ApoE4) contributes to sporadic, non-amyloid CSVD remains unclear. Previous literature has often inferred CSVD mechanisms from Alzheimer’s dis...

APOE2 attenuates APOE4-associated amyloid pathology and related toxicity in a mouse model of Alzheimer’s disease

The apolipoprotein E (APOE) gene is the strongest genetic risk factor for Alzheimer’s disease (AD), influencing amyloid-β (Aβ) aggregation, clearance, and glial function. While APOE4 promotes Aβ pathology and APOE2 is protective, how these opposing alleles interact in the heterozygous APOE2/4 state remains unknown. Her...

Progressive behavioral and cognitive decline in Drosophila harboring AD-associated APOE4 variants

A scalable model to dissect APOE-dependent mechanisms and identify therapeutic targets in AD is established, establishing a scalable model of disease pathogenesis and highlighting a central role for oxidized lipid metabolism in AD.

Serpin A3 is Increased in Cerebral Amyloid Angiopathy and ARIA

The role of vascular factors in Alzheimer's disease: from cerebrovascular pathological mechanisms to blood biomarkers

Alzheimer's disease (AD) is the most common dementia, and post-mortem and imaging studies consistently demonstrate that vascular pathology coexists with plaques and tangles in most AD brains. Vascular risk factors—hypertension, diabetes, dyslipidaemia, and atrial fibrillation—damage the neurovascular unit, disrupt the...

Astrocytic synapse engulfment is differentially controlled by APOE genotype.

APOE gene variants encoding the apolipoprotein E (ApoE) protein are strong genetic modifiers of risk of Alzheimer's disease (AD) with the APOE ε4 allele (APOE4) associated with substantially increased disease risk, APOE ε2 allele (APOE2) associated with decreased risk and APOE ε3 allele (APOE3) considered neutral. Rece...