Piura, Yoav

Abstract INTRODUCTION Plasma p‐tau217 and p‐tau217/Aβ42 reliably identify non‐Hispanic White individuals with symptomatic and pre‐clinical AD. However, performance across ethnoracially diverse groups remains unknown. METHODS Cognitively normal Black, Hispanic, and non‐Hispanic White participants completed cognitive evaluations, brain magnetic resonance imaging (MRI), amyloid and tau positron emission tomography (PET), and measures of kidney function. Plasma p‐tau217 and Aβ42 were measured using Fujirebio Lumipulse assays. Pre‐clinical AD detection was evaluated using symptomatic and cohort‐derived optimized cutoffs. RESULTS Among 191 participants (57 Black, 46 Hispanic White, 88 non‐Hispanic White), age‐adjusted plasma p‐tau217 and p‐tau217/Aβ42 performed similarly in detecting amyloid‐positive individuals (≥ 25 Centiloids), regardless of race/ethnicity. Both measures independently correlated with amyloid deposition, whereas estimated glomerular filtration rate (eGFR) correlated solely with p‐tau217. Pre‐clinical AD optimized cutoffs (p‐tau217 ≥ 0.132 pg/ml; p‐tau217/Aβ42 ≥ 0.0059) outperformed cutoffs established in symptomatic individuals (sensitivity: 83% vs. 57%; 77% vs. 63%; negative predictive value [NPV] > 93%). DISCUSSION Plasma biomarkers performed similarly across ethnoracially diverse cohorts. Optimized cutoffs may improve early detection and trial enrollment.

Background Reliable biomarkers of inflammatory activity in multiple sclerosis (MS) are needed to complement clinical and MRI assessments. Circulating microRNAs (miRNAs) are promising candidates due to their serum stability and involvement in MS-related biological pathways. Objectives To evaluate whether selected serum miRNAs can discriminate relapse from remission in treatment-naive patients with relapsing-remitting MS (RRMS). Methods In this prospective paired study, newly diagnosed, untreated RRMS patients were sampled during clinical relapse and subsequent remission. A targeted miRNA panel was quantified using quantitative PCR. Differential expressions were assessed using paired statistical testing with multiple comparison correction. Diagnostic performance was evaluated using ROC analysis and multivariate logistic regression. Pathway enrichment analysis was performed using Ingenuity Pathway Analysis. Results Twenty patients (40 paired samples) were included. Eight miRNAs were differentially expressed between relapse and remission after Benjamini–Hochberg correction. hsa-miR-122-5p showed the largest fold change (fold change = 3.0; adjusted p = 0.043). A three-miRNA panel (hsa-miR-122-5p, hsa-miR-15b-5p, hsa-miR-30e-5p) demonstrated high discriminative accuracy (area under the curve = 0.88; 95% CI 0.79–0.96). Pathway analysis highlighted inflammatory, metabolic, and hypoxia-related processes. Conclusions Circulating miRNAs distinguished relapse from remission in treatment-naive RRMS patients, suggesting their potential as complementary biomarkers of disease activity. These findings should be considered exploratory and require validation in an independent, larger cohort.

ABSTRACT Early identification of patients with treatment‐responsive rapidly progressive dementia (RPD) is important as early treatment improves outcomes. The STAM 3 P score identifies treatment‐responsive RPD using “high risk” presenting features. We optimized performance by adding a time component (i.e., dementia within 3 months) and validated the modified “STAM3 m P score” in two independent cohorts ( n = 302). A STAM3 m P score ≥ 1 identified 96% of patients with treatment‐responsive RPD; ≥ 3 features were highly specific (98%). These data suggest that ≥ 1 STAM3 m P features effectively identifies treatment‐responsive RPD and may be used to prioritize investigations, whereas ≥ 3 STAM3 m P features are highly specific and may inform early treatment decisions.