THE DISADVANTAGE EXPOSOME AS A DRIVER OF ALZHEIMERâS DISEASE PATHOLOGY - 1 PROJECT SUMMARY 2 ALZHEIMER'S…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_K00AG097172_075
- FAIN
- K00AG097172
- Recipient
- REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $169,369
- Period
- Sep 15, 2022 – May 31, 2029
- Fiscal year
- 2025
- Place of performance state
- CA
- Source file
- FY2025_All_Assistance_Full_20261006.zip
Description
THE DISADVANTAGE EXPOSOME AS A DRIVER OF ALZHEIMERâS DISEASE PATHOLOGY - 1 PROJECT SUMMARY 2 ALZHEIMER'S DISEASE (AD) IS THE MOST COMMON FORM OF DEMENTIA WORLDWIDE, INCURRING A PROJECTED HEALTHCARE 3 BURDEN OF $1 TRILLION IN THE UNITED STATES ALONE BY 2060. IT IS THE 7TH LEADING CAUSE OF MORTALITY IN THE UNITED STATES 4 AND IT DISPROPORTIONATELY IMPACTS MINORITIZED RACIAL AND ETHNIC GROUPS. ALTHOUGH MANY PHARMACOLOGIC 5 THERAPEUTICS HAVE BEEN TESTED TO SLOW OR REMOVE THE HALLMARK AMYLOID AND TAU AGGREGATES, NONE HAVE PROVED 6 EFFECTIVE AT REVERSING AD COGNITIVE DECLINE. THUS, THERE REMAINS URGENCY TO IDENTIFY FACTORS THAT CONTRIBUTE TO 7 DEMENTIA RISK AND NOVEL APPROACHES TO INTERVENE. WITH KNOWN CORRELATIONS TO CONDITIONS THAT INCLUDE GUT MICROBIAL 8 DYSBIOSIS AND EXPOSURE TO SOCIOCONTEXTUAL FACTORS THAT INCREASE DEMENTIA RISK, SUCH AS NEIGHBORHOOD 9 DISADVANTAGE, AD MAY BE PREVENTABLE OR TREATABLE AT SEVERAL POINTS OF INDIVIDUAL- AND COMMUNITY-LEVEL 10 INTERVENTION. HOWEVER, THE EXACT MECHANISMS BY WHICH THESE FACTORS CAN CONTRIBUTE TO AD ARE UNKNOWN. OUR 11 GROUP WAS FIRST TO IDENTIFY GUT MICROBIOME ALTERATIONS IN AD, AND SUBSEQUENT STUDIES IN HUMANS AND MOUSE 12 MODELS HAVE CORRELATED AD PATHOLOGY WITH MICROBIAL COMPONENTS AND ASSOCIATED INCREASES IN PERIPHERAL AND 13 CENTRAL INFLAMMATION. EXPOSURE TO NEIGHBORHOOD DISADVANTAGE IS SIMILARLY RELATED TO BOTH AD PATHOLOGY/COGNITIVE 14 DECLINE AND TO INFLAMMATORY PROFILES. IN FACT, EXAMINING HEALTH OUTCOMES LINKED TO THE GUT MICROBIOME AND 15 NEIGHBORHOOD DISADVANTAGE MORE BROADLY REVEALS SHARED ALTERATIONS IN INFLAMMATION, METHYLATION PROFILES, AND 16 RISK FOR CARDIOVASCULAR DISEASE. THESE ARE ALL COMORBID RISK FACTORS FOR AD, BEGGING THE QUESTION AS TO THE ROLE OF 17 NEIGHBORHOOD ENVIRONMENT IN ALTERING GUT MICROBIOTA COMPOSITION AND SUBSEQUENTLY EXACERBATING AD PATHOLOGY. 18 STUDIES OF GEOGRAPHY AND HOUSEHOLD SOCIAL RELATIONSHIPS SHOW AN EFFECT ON MACRO- AND MICRO-ENVIRONMENT ON 19 MICROBIAL COMPOSITION, HO