Alzheimer's Research & Therapy最新文献

Introduction: Alzheimer's disease (AD) is the leading cause of dementia in China, but deeply phenotyped clinical cohorts remain limited. The Biomarker and Clinical changes across the Alzheimer's continuum Study (BCAS) was established at the First Affiliated Hospital, Zhejiang University School of Medicine to capture biological and clinical changes across the AD spectrum.

Methods: BCAS is an ongoing, longitudinal memory clinic-based cohort initiated in 2016 in Zhejiang, one of China's most economically vigorous and rapidly aging regions. Individuals aged ≥ 40 years with cognitive concerns are recruited and undergo standardized clinical evaluation, comprehensive neuropsychological testing, biospecimen collection, and multimodal neuroimaging including MRI and amyloid and tau PET in subsets. Participants are followed every 1-2 years with repeat assessments. This paper reports baseline characteristics and preliminary findings from the first 1,013 participants enrolled up to January 2025.

Results: Participants had a mean age of 66.5 years (SD 9.6), with 49.8% women and an average of 9.7 years of education. Hypertension (41.4%), diabetes (14.6%), and hypercholesterolemia (12.0%) were the most prevalent comorbidities. The mean MoCA score was 19.2 (SD 6.1). Mean cognitive scores showed gradient decline across diagnostic groups from cognitively unimpaired, mild cognitive impairment to dementia, consistent with expected disease severity. Tau PET positivity showed a numerically larger cognitive z-score difference (-0.973 for T + vs. T-) compared with amyloid PET positivity (-0.530 for A + vs. A-). Among risk factors, higher age and diabetes were linked to lower scores, whereas higher education, tea consumption, and higher BMI were associated with better cognitive performance.

Conclusions: The BCAS served as a biomarker-rich and multimodal resource to study the clinical and biological progression of AD in China. Preliminary analyses demonstrate expected associations and support the data quality. BCAS will act as a platform for biomarker validation and precision approaches to AD diagnosis and intervention.

Tau pathology is a defining feature of Alzheimer's disease (AD), with hyperphosphorylated Tau (p‑Tau) emerging as a central biomarker for early diagnosis and disease monitoring. Various p‑Tau epitopes have demonstrated superior diagnostic precision and now form the molecular basis of updated AD diagnostic frameworks. Classical immunoassays such as enzyme-linked immunosorbent assay (ELISA), chemiluminescent enzyme immunoassay (CLEIA), and single molecule array (SIMOA) remain central to fluid based detection, offering high sensitivity and clinical validation. Recent advances in tau biology, especially in post-translational modifications, have driven the development of next generation biosensors. Electrochemical, optical, and nanostructured platforms now enable real-time, label-free, and attomolar level detection of p‑Tau in biofluids and live cell models. These systems are increasingly portable and suitable for point of care or in vivo applications. This review highlights the evolution of p‑Tau detection technologies, from benchmark immunoassays to cutting edge biosensors. Special attention is given to advanced affinity reagents, including aptamers, synthetic peptides, and antibody mimetics, which enhance biosensor specificity, stability, and translational potential. Together, these innovations are redefining AD diagnostics, enabling early intervention and more effective disease monitoring.