Super-Resolution Imaging Uncovers Nanoscale Tau Aggregate Hyperphosphorylation Patterns in Human Alzheimers Disease Brain Tissue

crossref(2024)

引用 0|浏览4
暂无评分
摘要
Tau aggregation plays a critical role in Alzheimer's Disease (AD), where tau neurofibrillary tangles (NFTs) are a key pathological hallmark. While much attention has been given to NFTs, emerging evidence underscores nano-sized pre-NFT tau aggregates as potentially toxic entities in AD. By leveraging DNA-PAINT super-resolution microscopy, we visualized and quantified nanoscale tau aggregates (nano-aggregates) in human postmortem brain tissues from intermediate and advanced AD, and Primary Age-Related Tauopathy (PART). Nano-aggregates were predominant across cases, with AD exhibiting a higher burden compared to PART. Hyperphosphorylated tau residues (p-T231, p-T181, and p-S202/T205) were present within nano-aggregates across all AD Braak stages and PART. Moreover, nano-aggregates displayed morphological differences between PART and AD, and exhibited distinct hyperphosphorylation patterns in advanced AD. These findings suggest that changes in nano-aggregate morphology and hyperphosphorylation patterns may exacerbate tau aggregation and AD progression. The ability to detect and profile nanoscale tau aggregates in human brain tissue opens new avenues for studying the molecular underpinnings of tauopathies.
更多
查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要