👤 Carmen R Isasi

Apolipoprotein E (APOE) alleles are well-established genetic risk factors for Alzheimer's disease (AD), but their effects on AD biomarkers (amyloid beta [Aβ]42/40, phosphorylated tau [p-tau]181, neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]) may vary across populations due to ancestry-, age-, and sex-related differences. We hypothesized that these effects vary across Hispanic/Latino background groups with distinct ancestral admixture. We analyzed ε2 and ε4 allele associations with AD biomarkers using survey-weighted linear regression models, adjusting for demographic covariates. Secondary analyses examined genetic analysis group- and ancestry-specific effects. ε4 was associated with lower Aβ42/40 and higher p-tau181and GFAP levels, but not with NfL, suggesting its role in Aβ and tau deposition and neuroinflammation. ε4 associations were stronger in those with higher European and lower African ancestry. These findings expand on prior studies suggesting that genetic ancestry modifies APOE-associated AD risk in Hispanic/Latino populations and highlight the importance of capturing ancestry-based heterogeneity in AD biomarker research. Show less

The purpose of this study was to estimate the prevalence and number of cerebral microbleeds (CMBs) in a Hispanic and Latino cohort from various self-identified backgrounds and test associations with age, vascular risk factors, APOE (apolipoprotein E), and cognitive function. The 3T brain magnetic resonance imaging exams were obtained on SOL-INCA-MRI (Study of Latinos-Investigation of Neurocognitive Aging-MRI) magnetic resonance imaging study participants, a community-based study. CMB number was counted and categorized as: (1) any CMB, (2) lobar only, (3) deep only, (4) mixed, (5) deep+mixed, and (6) lobar+mixed. We examined whether prevalence of CMBs varied by age, sex, education, Hispanic background, cardiovascular risk factors (hypertension, diabetes, Framingham Risk Score), APOE genotype, and cognition. A total of 2455 participants were included who were 63.0±8.4 years of age, 67.9% women, and 62.2% high school education or higher. CMBs prevalence was 11.7% (8.3% lobar only, 2.0% deep only, 1.4% mixed locations). After adjusting for age, sex, and education, a high Framingham Risk Score was associated with the presence of CMBs of all types, except lobar only. Prevalent stroke/transient ischemic attack was associated with higher likelihood of deep-only CMBs. For participants with cognitive impairment, the adjusted prevalence of mixed CMBs (2.2% versus 1.1%, High vascular risk scores, self-reported history of stroke/transient ischemic attack, and cognitive status were associated with a higher likelihood of CMBs, especially in deep regions. Show less

Blood-based biomarkers hold promise as a minimally invasive tool for identifying early signs of Alzheimer's disease pathology and neurodegeneration. We investigated associations between plasma biomarkers of amyloid-beta, tau, neuroaxonal injury, and glial activation with cognitive performance among community-dwelling Hispanic/Latino adults in the United States. We analyzed cross-sectional data from 5730 adults aged 50 years and older (unweighted; mean [SD], 63.5 [8.2] years) in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA; 2016-2018). Plasma concentrations of amyloid-beta (Aβ Here we show higher ln(pTau-181) and ln(NfL) are associated with lower global cognitive performance (b Plasma biomarkers related to Alzheimer's disease pathophysiology and broader neurodegenerative processes are associated with cognitive performance among Hispanic/Latino adults. These findings highlight the potential utility of blood-based biomarkers for identifying early cognitive vulnerability in this population. Show less

The effect of genetic variation on plasma lipoproteins and their subfraction distribution was examined. Forty Hispanic men and 223 women and 42 non-Hispanic white men and 53 women participated in the study. Genotypes for cholesteryl ester transfer protein (CETP TaqIB), hepatic lipase (LIPC -480 C > T), lipoprotein lipase (LPL S447X), and apolipoprotein CIII (APOC3--455T > C) were determined by polymerase chain reaction. Lipoprotein particle size distribution was determined by nuclear magnetic resonance. For all but APOC3, genotype effects were homogeneous in the ethnic/racial groups and men and women. Effects were seen primarily in the women. Compared to women carriers of the common CETP B1 allele, B2B2 women had significantly higher plasma levels of high-density lipoprotein cholesterol (HDL-C) (16.4.0%, p = 0.001), reflected in the level of larger HDL particles (21.9%, p = 0.001), and larger mean particle size of HDL (2.3%, p = 0.01) and low-density lipoproteins (LDL) (1.3%, p = 0.02). Compared to LPL 447S homozygous women carriers of the LPL 447X allele had significantly lower levels of very-low-density lipoprotein-triglyceride (VLDL-TG) (21.0%, p = 0.02). For APOC3, there was significant gender:genotype interaction with the genotype differences seen only in the men. Compared to men homozygous for the -455T allele, carriers of -455C had higher levels of VLDL-TG (71.4%, p = 0.0001), reflected in a larger mean VLDL particle size (13.7%, p = 0.009). LIPC genotype was not associated with significant effects on any of these traits. These data confirm the role of genetic variants of CETP, LPL and APOC3 in determining the relationship between VLDL, LDL and HDL particles. Show less

To examine the genotype:phenotype association in children compared with their parents. Variations at 4 key gene loci, namely lipoprotein lipase (LPL S447X), hepatic lipase (HL -480C>T), cholesteryl ester transfer protein (CETP TaqIB), and apolipoprotein CIII (APOC3 -455T>C and -482C>T), were examined in children (n = 495) and their parents (n = 353) in the Columbia University BioMarkers Study, 1994 to 1998. The frequencies of the rare alleles of the HL -480C>T and APOC3 -455T>C and -482C>T (but not LPL S447X or CETP TaqIB) were significantly lower in non-Hispanic white participants compared with Hispanics. Overall, genotype effects seen in the adults were weaker in the children, although similar trends were seen. In an examination of the effect of body fat on the genotypic effects in the children, there was significant HL -480C>T:sum of skinfold interaction. All genotypes were associated with clear relationships to plasma lipid levels in adults, but the effects were weaker in their children, unless stressed by body fat. atherosclerosis, cardiovascular disease, child, lipids, genetics. Show less