👤 Corey T McMillan

This study aimed to compare positron emission tomography (PET) and plasma-based temporal modeling of amyloid and tau biomarkers in Alzheimer's disease. Longitudinal amyloid PET (n = 1,097, mean age ± SD = 72.5 ± 7.38 year, 51.4% male), Plasma and PET models generated similar results for estimated amyloid and tau onset, with stronger model agreement for tau (r = 0.88[0.86, 0.89], t = 57.4, p < 0.001) than amyloid (r = 0.75[0.72, 0.77], t = 37.4, p < 0.001) onset. Accuracy of estimated onset compared to actual onset was high within modality (mean absolute error [MAE] ≤ 2.03) with slightly greater error (MAE 3.09-3.42) when comparing across modalities (ie, plasma to PET). For both plasma and PET, earlier tau onset was associated with younger amyloid onset, female sex, and ≥1 apolipoprotein (ApoE) ε4 allele. Earlier dementia onset after tau was associated with later tau onset for both plasma and PET, while male sex was associated with shorter tau to dementia gap in plasma models. Temporal modeling of plasma biomarkers provides comparable information to PET-based models, particularly for tau onset age, and can serve as a widely accessible tool for clinical assessment of biological disease severity. ANN NEUROL 2026. Show less

Plasma biomarkers of Alzheimer's disease (AD) pathology are frequently tested in specialized research settings, which limits the generalizability of findings. Using electronic health records and banked plasma, we evaluated plasma biomarkers-phosphorylated tau 217 (p-tau Participants (n = 617; 44% Black/African American; 41% female) were selected from the University of Pennsylvania Medicine BioBank with plasma assayed using Fujirebio Lumipulse. International Classification of Diseases (ICD) Ninth and Tenth Revision codes determined AD dementia (ADD) (n = 43), mild-cognitive impairment (MCI) (n = 140), unspecified/non-AD cognitive impairment (CI) (n = 106), and cognitively normal cases (n = 328), and other medical histories. APOE ε4, body mass index (BMI), metrics of kidney function (eg, estimated glomerular filtration rate [eGFR]), and liver disease were derived from electronic health records. Multivariable models identified factors related to plasma levels. Previously established cutpoints classified AD status ("AD+," "AD-," or "Intermediate"). Plasma p-tau In this real-world dataset, we identified effects of multimorbidities on plasma biomarkers, especially kidney function. The p-tau Show less

To execute a large-scale, decentralized, clinical-grade whole exome sequencing study, coined Tapestry, for clinical practice, research discovery, and genomic education. Between July 1, 2020, and May 31, 2024, we invited 1,287,608 adult Mayo Clinic patients to participate in Tapestry. Of those contacted, 114,673 patients were consented and 98,222 (65.2% women) are currently enrolled: 62,495 (63.6%) were recruited from Minnesota-, 18,353 (18.7%) from Florida- and 17,374 (17.7%) from Arizona-based practices. Saliva from participants was used to extract DNA, and whole exome sequencing plus ∼300,000 single nucleotide polymorphisms (ie, Exome+ assay) were sequenced by a clinical lab. Results for the Centers for Disease Control and Prevention Tier 1 genes (eg, hereditary breast, ovarian cancer syndrome: BRCA1/2; Lynch syndrome: MLH1, MSH2, MSH6, PMS2, and EPCAM; and familial hypercholesterolemia: APOB, LDLR, PCSK9, and LDLRAP1) were interpreted and entered into the electronic health record. The median age of participants was 59.1 years and ∼11% were from racial/ethnic groups under-represented in research. One thousand eight hundred nineteen (1.9%) participants had actionable pathogenic or likely pathogenic variants (50.0% BRCA1/2, 28.4% familial hypercholesterolemia, and 22.2% Lynch syndrome). Positive results were communicated by genetic counselors who educated patients and providers. Thus far, 62,758 patients' Exome+ assays are stored for research, and the Tapestry Data Access Committee has received 118 requests from investigators, of which 82 have been approved, resulting in the delivery of 1,117,410 Exome+ assays to researchers. A large, decentralized, clinical Exome+ assay study in a tertiary medical center detects actionable germline variants, educates patients as well as providers, and offers access to big data for discovery that advances human health. clinicaltrials.gov Identifier: NCT05212428. Show less

Gastrointestinal hormone based therapies are being investigated for treating diabetes in cats; however, the tissue distribution of these hormones and their cognate receptors remain largely understudied. We determined the distribution of transcripts for the gut hormones proglucagon (Gcg), glucose-dependent insulinotropic peptide (Gip), peptide YY (Pyy), and their receptors (Glp1r, Gipr, Npy2r), in feline peripheral tissues. The Gcg, Gip and Pyy mRNA were expressed in the gut, with higher Gcg and Pyy abundance in the lower gut. Interestingly, Glp1r and Npy2r mRNA were expressed in multiple peripheral tissues including the gut, pancreas and liver, whereas, Gipr mRNA was restricted to the stomach and adipose tissues. The localized mRNA expression of Gcg and Pyy in the gut, but the extensive distribution of Glp1r and Npy2r in several peripheral tissues suggests that these hormones may have pleiotropic physiological functions in cats. Show less