Plasma and CSF biomarkers for Alzheimer’s disease among Caribbean Hispanics

Abstract

AbstractBackgroundBiomarkers provide earlier and more accurate diagnoses of Alzheimer’s disease (AD). Cerebrospinal fluid (CSF) biomarkers have proven highly specific and sensitive in research studies (e.g. ADNI, BIOFINDER), although often including mostly well‐educated, white non‐Hispanics without co‐morbidities. CSF testing also requires lumbar puncture, so blood testing would be of great value. Here we examined a Caribbean Hispanic cohort, with measurements of both plasma and CSF biomarkers of amyloid (Aβ42, Aβ40), tau (p‐tau181), and neurodegeneration (t‐tau, NfL).MethodStudy cohort included individuals of Caribbean Hispanic ancestry (N = 123; 45 [37%] men, 78 [63%] women) enrolled in the Dominican Republic or New York City, who underwent venipuncture, lumbar puncture, and neurological assessments. Average age was 69.5 yr (sd 8.0; range 45‐91); APOE e4 genotypes were 50% without e4, 30.2 % e4 heterozygous, and 19.8% e4 homozygous. Clinical diagnoses included non‐demented (54%), mild cognitive impairment (MCI, 21%), and dementia (25%). No individuals had non‐AD dementias, so MCI and dementia were combined as “AD” (46%). Samples were stored at ‐80C, and assayed in duplicate (average coefficients of variation 4‐7%) on the Simoa SR‐X platform (Quanterix), using Neurology 3‐Plex A kits for Aβ42, Aβ40, and t‐tau, and separate assay kits for p‐tau181 and NfL. Ratios of Aβ42/Aβ40, t‐tau/Aβ42, and p‐tau181/Aβ42 were also calculated. Regression and ROC analyses were performed, including models adjusting for age, gender, and number of APOE e4 alleles, using IBM SPSS 27.ResultOverall, individuals with AD showed elevated levels of both plasma and CSF t‐tau, p‐tau181, and NfL. There was significant correlations between plasma and CSF for p‐tau181 (r=0.45, p<0.0001), for NfL (r=0.62, p<0.0001), and for plasma ratios Aβ42/Aβ40 (r=0.33, P<0.001), t‐tau/Aβ42(r=0.34, p<0.001) and p‐tau181/Aβ42 (r=0.39, p<0.0001) but not for plasma Aβ40, Aβ42, or t‐tau individually. Plasma analytes performed moderately well, especially p‐tau181 and NfL, better than CSF, in classifying persons with cognitive impairment, with ROC areas under the curve (AUC) of 74.4% and 73.2% respectively. Plasma ratios of Aβ42/Aβ40, t‐tau/Aβ42, and p‐tau181/Aβ42 did not perform as well.ConclusionPlasma p‐tau181 and NfL biomarkers performed well in classifying AD, in comparison to CSF biomarkers, in this Caribbean Hispanic cohort.