Large-scale plasma proteomic profiling identifies a high-performance biomarker panel for Alzheimer's disease screening and staging

INTRODUCTION: Blood proteins are emerging as candidate biomarkers for Alzheimer's disease (AD). We systematically profiled the plasma proteome to identify novel AD blood biomarkers and develop a high-performance, blood-based test for AD. METHODS: We quantified 1160 plasma proteins in a Hong Kong Chinese cohort by high-throughput proximity extension assay and validated the results in an independent cohort. In subgroup analyses, plasma biomarkers for amyloid, tau, phosphorylated tau, and neurodegeneration were used as endophenotypes of AD. RESULTS: We identified 429 proteins that were dysregulated in AD plasma. We selected 19 “hub proteins” representative of the AD plasma protein profile, which formed the basis of a scoring system that accurately classified clinical AD (area under the curve = 0.9690–0.9816) and associated endophenotypes. Moreover, specific hub proteins exhibit disease stage-dependent dysregulation, which can delineate AD stages. DISCUSSION: This study comprehensively profiled the AD plasma proteome and serves as a foundation for a high-performance, blood-based test for clinical AD screening and staging

Genetic and polygenic risk score analysis for Alzheimer's disease in the Chinese population

Introduction: Dozens of Alzheimer's disease (AD)-associated loci have been identified in European-descent populations, but their effects have not been thoroughly investigated in the Hong Kong Chinese population. Methods: TaqMan array genotyping was performed for known AD-associated variants in a Hong Kong Chinese cohort. Regression analysis was conducted to study the associations of variants with AD-associated traits and biomarkers. Lasso regression was applied to establish a polygenic risk score (PRS) model for AD risk prediction. Results: SORL1 is associated with AD in the Hong Kong Chinese population. Meta-analysis corroborates the AD-protective effect of the SORL1 rs11218343 C allele. The PRS is developed and associated with AD risk, cognitive status, and AD-related endophenotypes. TREM2 H157Y might influence the amyloid beta 42/40 ratio and levels of immune-associated proteins in plasma. Discussion: SORL1 is associated with AD in the Hong Kong Chinese population. The PRS model can predict AD risk and cognitive status in this population

Age and Growth of the Scalloped Hammerhead, Sphyrna lewini, in Northeastern Taiwan Waters

Age and growth of the scalloped hammerhead, Sphyrna lewini, caught mostly by longline and harpoon in northeastern Taiwan waters from December 1984 to November 1985, were determined from annulus counts from 325 individuals. Translucent and opaque zones on vertebral centra were formed twice a year, in June and December. The von Bertalanffy growth curve parameters obtained using a nonlinear regression based on age and observed length were as follows: asymptotic length (Loo) = 319.72 cm total length (TL), growth coefficient (K) = 0.249, age at zero length (to) = - 0.413 yr for females; and Loo = 320.59 cm TL, K = 0.222, to = - 0.746 yr for males. Growth was apparently fast and varied among individuals. Growth rate s for females were estimated to be 63cm for the first year, 23-50 cm/yr for years 2-5, and 3-19 cm/yr for years 6-13. Growth rates for males was 54 cm for the first year, 22-42 cm/yr for years 2-5, and 11-18 cm/yr for years 6-8. Holden's method was applied to estimate growth parameters for purposes of comparison. Estimated age at maturity was 4.lyr (210cmTL) for females and-3:8yr (198cm-TL) for males, based on the von Bertalanffy growth equation from back-calculated data. The largest female (331 cm TL) whose age was determined in this study was 14.0 yr old; the largest male (301 cm TL) was 10.6 yr old

Large‐scale plasma proteomic profiling identifies a high‐performance biomarker panel for Alzheimer's disease screening and staging

INTRODUCTION: Blood proteins are emerging as candidate biomarkers for Alzheimer's disease (AD). We systematically profiled the plasma proteome to identify novel AD blood biomarkers and develop a high-performance, blood-based test for AD. METHODS: We quantified 1160 plasma proteins in a Hong Kong Chinese cohort by high-throughput proximity extension assay and validated the results in an independent cohort. In subgroup analyses, plasma biomarkers for amyloid, tau, phosphorylated tau, and neurodegeneration were used as endophenotypes of AD. RESULTS: We identified 429 proteins that were dysregulated in AD plasma. We selected 19 “hub proteins” representative of the AD plasma protein profile, which formed the basis of a scoring system that accurately classified clinical AD (area under the curve = 0.9690–0.9816) and associated endophenotypes. Moreover, specific hub proteins exhibit disease stage-dependent dysregulation, which can delineate AD stages. DISCUSSION: This study comprehensively profiled the AD plasma proteome and serves as a foundation for a high-performance, blood-based test for clinical AD screening and staging

Adaptive cluster sampling with a data driven stopping rule

Adaptive cluster sampling, Monte carlo simulation, Stopping rule, Efficiency,