Identification of endothelial gene targets over alzheimer s disease progression

The National Institute on Aging awarded Albany Medical College $451,000 on September 1, 2026, under the Aging Research program (CFDA 93.866) to identify endothelial gene targets over Alzheimer's disease progression.

The research investigates alterations in brain endothelial translatome in Alzheimer's disease and vascular pathology across the progression timeline and in both sexes, addressing a gap in prior studies that were predominantly male or sex-unstratified. The project uses two Alzheimer's disease mouse models to capture a broader range of Alzheimer's disease and related dementias pathology, assessing endothelial translatome at early, mid, and late timepoints. Gene changes will be correlated with Alzheimer's disease and related dementias pathology and cognitive function. The study integrates endothelial translatome data with real-time functional data throughout disease progression to identify potential sex-specific modifiable targets at both preventative and interventional stages. Over 80 percent of Alzheimer's disease patients exhibit vascular pathology, and vascular risk factors accelerate cognitive decline independent of amyloid pathology. Women comprise two-thirds of those with Alzheimer's disease, and sex differences in genetic risk for the disease remain understudied.

The period of performance runs from September 1, 2026, through August 31, 2028. Work is performed at Albany Medical College in Albany, New York.

Abstract

Over 80% of alzheimer's disease (ad) patients exhibit vascular pathology. Vascular risk factors accelerate cognitive decline as well as the progression of ad independent of amyloid pathology. Human ad endothelial transcriptomic studies are often limited to one late-timepoint, overlooking potential early targets. However, even when limited to one timepoint, these human studies demonstrate significant changes in vascular genes with ad. Unfortunately, prior studies were either performed in males, or not stratified by SEX. Thus, changes in females are unknown. SEX plays an important role in ad, as 2/3 of those with ad are women. Importantly, men and women also differ in their genetic risk for ad. We will overcome limitations of previous studies by investigating alterations in brain endothelial translatome, in ad, over a time course of ad pathology in each SEX. We aim to investigate alterations in brain endothelial translatome in ad and vascular pathology, over a time course of ad progression and in both sexes. We will utilize two ad mouse models to capture a greater range of ad and related dementias (adrd) pathology. The endothelial translatome will be assessed at an early, mid, and late timepoint and gene changes correlated with adrd pathology and cognitive function. We will integrate endothelial translatome data with real time functional data, throughout the progression of ad pathology, to uncover potential SEX-specific modifiable targets at both a preventative stage and an interventional stage.