Pereira, Ana C.

Abstract INTRODUCTION Apolipoprotein E allele 4 (APOE ε4) is the main genetic risk factor for late‐onset Alzheimer's disease (AD), but most evidence comes from White populations in high‐income countries. We investigated APOE and AD pathology in an ethnically diverse Brazilian autopsy cohort. METHODS This cross‐sectional study used Biobank for Aging Studies (BAS) data. AD pathology was evaluated with Braak, Consortium to Establish a Registry for Alzheimer's Disease, and Thal criteria. APOE genotypes were obtained from blood or brain tissue. Regression models were adjusted for age, sex, race, and education; interaction with race was tested. RESULTS Among 1391 participants (mean age 75.1 ± 12.4 years, 50% women, 64% White), APOE ε4showed a dose response with greater AD pathological burden and higher odds of AD diagnosis, while APOE ε2/X was protective. APOE ε4/ε4 did not show full penetrance across age groups. Associations were similar in White and Black individuals. DISCUSSION APOE ε4was strongly associated with AD pathology, with consistent associations across racial groups. Highlights APOE ε4 increased AD neuropathological burden in Brazilians. APOE ε2/εX was protective against AD pathology. APOE ε4/ε4did not show full penetrance across age groups. Associations between APOE and AD pathology were similar by race. Large multiethnic autopsy study expands evidence beyond high‐income country studies.

Abstract INTRODUCTION Clinicians’ views on the clinical readiness of Alzheimer's disease (AD) blood biomarkers (BBMs) are not well understood. METHODS The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment Biofluid‐Based Biomarkers Professional Interest Area conducted a survey to elicit clinician opinions on AD BBM implementation, including contexts of use, assay selection, reporting, and result interpretation. RESULTS Clinician respondents ( n = 212) practiced in Europe (56%), North America (24%), the Caribbean and Central/South America (11%), and other continents (9%). Most respondents were medical doctors (80%) practicing in secondary or tertiary care (88%). For 56%, cerebrospinal fluid AD biomarkers or amyloid positron emission tomography were accessible, but 48% agreed and 52% disagreed with the implementation of AD BBMs in any clinical context. Respondents emphasized the need for data from diverse populations and educational resources to support test interpretation. DISCUSSION Surveyed clinicians generally agreed with published appropriate use recommendations but were divided on AD BBM readiness for clinical use. Highlights A survey of clinicians was conducted regarding clinical readiness of Alzheimer's disease (AD) blood biomarkers (BBMs). Views were split on AD BBM clinical readiness: 48% agreed, 52% disagreed. Most responders supported AD BBM use for treatment decisions. Most responders opposed AD BBM testing in asymptomatic individuals. Test performance data and educational materials to aid interpretation were of high importance.