Project Grant K99AG086530

ALZHEIMER'S DISEASE AND RELATED DEMENTIA NEUROPATHOLOGIES AND EXPOSURES TO TRAFFIC POLLUTION MIXTURES - PROJECT SUMMARY ALZHEIMER'S DISEASE (AD) AND RELATED DEMENTIAS (ADRD) ARE A GROWING CONCERN IN OUR AGING POPULATION. THE IDENTIFICATION OF MODIFIABLE RISK FACTORS IS CRITICAL. GROWING EVIDENCE LINKS ADRD TO TRAFFIC-RELATED AIR POLLUTION (TRAP), A COMPLEX MIXTURE OF GASSES AND PARTICLES THAT INCLUDES ULTRAFINE PARTICLES (UFP, 100 NM DIAMETER), BLACK CARBON (BC), OXIDES OF NITROGEN (NOX), FINE PARTICLES (PM2.5) AND OTHER POLLUTANTS. THE IMPACT OF TRAP MIXTURES AS A WHOLE (VS INDIVIDUAL POLLUTANTS) ON ADRD, THE MOST RELEVANT POLLUTANTS, AND CRITICAL EXPOSURE PERIODS, HOWEVER, HAVE NOT BEEN IDENTIFIED TO SUPPORT FUTURE EVIDENCE-BASED INTERVENTIONS AND REGULATIONS. MOREOVER, MOST EPIDEMIOLOGIC AIR POLLUTION STUDIES HAVE INVESTIGATED CLINICAL COGNITIVE OUTCOMES; FEW HAVE INVESTIGATED NEUROPATHOLOGIC CHANGES MORE CLOSELY TIED TO MECHANISMS. UFPS MAY HAVE AN INCREASED NEUROTOXIC POTENTIAL BECAUSE OF THEIR SMALL SIZE. UFP HEALTH STUDIES ARE LIMITED BECAUSE UFPS ARE NOT REGULARLY MONITORED, AND THEY REQUIRE NOVEL MONITORING TECHNIQUES. THE ADULT CHANGES IN THOUGHT (ACT) STUDY IS ONE OF THE LARGEST, MOST EXTENSIVE COMMUNITY-BASED AUTOPSY COHORTS IN THE WORLD. MY TEAM PREVIOUSLY DEVELOPED THE FIRST-OF-THEIR-KIND, UFP/TRAP EXPOSURE SURFACES USING AN INNOVATIVE MOBILE MONITORING DESIGN IN 2019 FOR THIS COHORT. I WILL APPLY MY EXPERTISE IN EXPOSURE SCIENCE DEVELOPING LONG-TERM TRAP MODELS AND UFP MONITORING CAMPAIGNS ALONG WITH NEW TRAINING IN ADRD NEUROPATHOLOGY, EXPOSURE MIXTURES, AND ADVANCED EPIDEMIOLOGIC METHODS TO ADDRESS THE FOLLOWING IMPORTANT GAPS. IN AIM 1, I WILL EVALUATE ASSOCIATIONS BETWEEN EXPOSURES TO UFP/TRAP MIXTURES AND LATE-LIFE ADRD NEUROPATHOLOGICAL CHANGES AT AUTOPSY AND DETERMINE WHETHER THESE EFFECTS ARE MAGNIFIED IN WOMEN, APOLIPOPROTEIN E (APOE) E4 CARRIERS, OR INDIVIDUALS WITH LOWER SOCIOECONOMIC STATUS. IN AIM 2, I WILL COLLECT ADDITIONAL UFP DATA AND DEVELOP THE FIRST LONG-TERM UFP EXPOSURE SURFACES. IN AIM 3, I WILL EVALUATE LONG-TERM UFP/TRAP EXPOSURES AND ADRD NEUROPATHOLOGIES; IDENTIFY THE EXPOSURE PERIODS THAT MAY BE MOST RELEVANT FOR THE DEVELOPMENT OF NEUROPATHOLOGIES; AND ADDRESS POTENTIAL SURVIVAL BIASES IN AUTOPSY STUDIES - A CONCERN THAT HAS RECEIVED SCANT EPIDEMIOLOGIC ATTENTION BUT MAY BE A CONCERN WHEN THE EXPOSURE OF INTEREST (E.G., AIR POLLUTION) INCREASES RISK OF DEATH (I.E., AUTOPSY) AT YOUNGER AGES WHEN NEUROPATHOLOGIES ARE NATURALLY LESS SEVERE. MY TRAINING PLAN, WHICH CONSISTS OF AN EXCELLENT MENTORSHIP TEAM OF INTERNATIONAL EXPERTS, SPECIFIC TRAINING GOALS, PROFESSIONAL DEVELOPMENT, AND TRANSITION TO INDEPENDENCE WILL POSITION ME TO SUCCESSFULLY DEVELOP THE SKILLS AND EXPERIENCES NEEDED TO LEAD THIS STUDY. I WILL BE UNIQUELY QUALIFIED TO DEVELOP A CAREER INDEPENDENTLY LEADING NOVEL AND ORIGINAL STUDIES IN THE FIELDS OF ADRD NEUROPATHOLOGIES AND ENVIRONMENTAL EXPOSURE MIXTURES.