Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Genetic and Proteomic Pathways Linking Alzheimer's Disease to White Matter Hyperintensities

Award Number: K01AG101395
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2031

Group Awards By:

View Award Description

Genetic and Proteomic Pathways Linking Alzheimer's Disease to White Matter Hyperintensities - The overlap of cerebral small vessel disease (cSVD) and Alzheimer’s disease (AD) in older adults creates a rising public-health crisis. Lesions called white matter hyperintensities (WMH) on brain scans have long been blamed on only small-vessel damage, but evidence links them to AD pathology too. Individuals with AD accumulate more WMH in the back of the brain, and carriers of AD-risk genes show WMH buildup long before memory loss begins even without cSVD risk factors. Fluid measurements of AD and neurodegeneration with AD- genetic focused studies also tie Alzheimer’s pathophysiological processes to WMH burden. African American older adults carry higher vascular risk yet lower measured brain amyloid, and they develop dementia more often—yet we know little about how AD pathology contributes to their WMH lesions. Literary evidence supports my hypothesis that AD genetic liability drives WMH burden via specific circulating protein mediators, and that ancestry-tuned polygenic risk scores integrating AD and WMH pathways will markedly improve prediction. To test the hypothesis, I will use high-dimensional biological data (genetics and plasma proteomic measures) combined with neuroimaging measures for WMH and advanced epidemiological/biostatistical methods in the UK Biobank and the Jackson Heart Study (JHS). In aim 1 (UK Biobank), I will quantify causal association between AD associated genes and WMH via two-sample Mendelian randomization using independent AD related genes as instruments and UKB WMH summary statistics as outcomes, with heterogeneity investigations by sex and ancestry. In aim 2 (UK Biobank), I will identify proteomic mediators of AD genetic risk in WMH using multivariable regression, cluster significant proteomic signatures to showcase underlying pathological mechanisms that contribute to WMH and use two-sample mediation Mendelian randomization to identify proteins that mediate the association between AD genes and WMH. In aim 3 (JHS), I will develop an African-ancestry–tuned WMH polygenic risk score informed by AD-related plasma neurobiomarkers. First, I will test the associations of plasma neurobiomarkers (Aβ42/40, phosphorylated tau-181, neurofilament light, and glial fibrillary acidic protein) and proteins with JHS-derived WMH volume. Secondly, I will perform two-sample Mendelian randomization with proteins and WMH genes to infer causality. Lastly, I will build three candidate WMH polygenic risk scores—two standard and one new, plasma neurobiomarkers-weighted—tuned to African ancestry, select the best performer by how much variance it explains, and validate it in three independent cohorts that include European, African, and Hispanic ancestry. The scientific training goals include developing expertise in 1) genetic epidemiologic methods; 2) advanced biostatistical methods for high dimensional biological data; 3) deepen expertise in AD and related dementias research. This mentored award will support me to establish an interdisciplinary laboratory that applies advanced epidemiological and biostatistical methods to high-dimensional biological data, revealing how cSVD and AD pathology jointly shape brain aging.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $125,766 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Aging Research	000	1	6/30/2026	NEW	$125,766
														Subtotal = $125,766

Grand Total All Awards = $125,766

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Genetic and Proteomic Pathways Linking Alzheimer's Disease to White Matter Hyperintensities

Award Number: K01AG101395

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer