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

SORL1 and its involvement in Alzheimer's disease pathogenesis and pathophysiology

Award Number: P01AG090268
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2025
PERIOD OF PERFORMANCE END DATE: 05/31/2030

Group Awards By:

View Award Description

SORL1 and its involvement in Alzheimer's disease pathogenesis and pathophysiology - OVERALL PROJECT SUMMARY/ABSTRACT SORL1 is emerging as only the 4th gene that is considered causal in Alzheimer’s disease. New insight shows how SORL1 functions by interacting with the retromer trafficking complex, how disrupting this interaction can mediate the disease’s cardinal pathologies, and how SORL1-retromer disruptions have been commonly linked to late-onset AD. The problem is that there are hundreds of disease-associated SORL1 variants, and the pathogenesis and pathophysiology of most of them remain unknown. The PPG’s overall goal is to solve this problem by relying on a recently developed prioritization framework designed to identify SORL1 missense variants most likely to be pathogenic. The framework uses the known effects of variants in proteins with similar domains to assess the likelihood that a SORL1 variant in a homologous domain may lead to a specific defect. As also detailed in the application, provisional support for this framework’s capabilities is provided by recent studies. The PPG’s overall approach is to rely on a unified set of SORL1 variants that the framework predicts to be pathogenic. The PPG’s Cores will provide biomaterials plus clinical and cellular evidence on the pathogenicity of each variant, using both standard and novel readouts. The Projects will collectively probe the pathophysiology of each of the pathogenic variants--- integrating structural, cellular, anatomical, and biofluidic investigations. The PPG’s Cores and Projects will have hypothesis-driven aims, building on existing evidence about how SORL1 loss-of-function variants affect the retromer-dependent endosomal recycling pathway, but they will also have unbiased aims designed to explore and expand the mechanistic understanding into how SORL1 might drive and/or modulate AD pathology. Collectively, by clarifying SORL1’s loss-of-function, the PPG promises to have high and broad translational impact. Ultimately, by completing the proposed studies, the PPG will inform on developing novel therapeutic interventions, not only for the estimated 3% of all AD patients who are thought to harbor a pathogenic SORL1 variant, but also for late-onset disease more generally.


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 = $3,187,703 )
2026	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	002	2	6/3/2026	NON-COMPETING CONTINUATION	$3,187,703
2026	2025	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	001	1	5/5/2026	NEW	$0
2026	2025	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	1	12/10/2025	NEW	$0
														Subtotal = $3,187,703

Issue Date FY: 2025 ( Subtotal = $3,184,272 )
2025	2025	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	1	9/5/2025	NEW	$3,184,272
														Subtotal = $3,184,272

Grand Total All Awards = $6,371,975

Top

All Categories

About

Search

Reports

Data Submission

Award Information

SORL1 and its involvement in Alzheimer's disease pathogenesis and pathophysiology

Award Number: P01AG090268

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/15/2025

PERIOD OF PERFORMANCE END DATE: 05/31/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer