期刊
JOURNAL OF NEUROSCIENCE
卷 42, 期 7, 页码 1352-1361出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1601-21.2021
关键词
aging; Alzheimer's disease; amyloid-beta; fMRI; PET; tau
资金
- National Institutes of Health [F31-AG-062090, F32-AG-057107, R01-AG-034570, R01-AG-062542]
- Tau Consortium
- Helmholtz Postdoc Grant [PD-306]
- Avid Radiopharmaceuticals
This study aimed to investigate the mechanisms underlying the initial accumulation of tau pathology and the predictive roles of age, AP, and neural activity in tau accumulation. The results showed that older age, higher neural activity, and higher baseline EC tau levels were associated with tau accumulation. Additionally, AP facilitated the spread of tau.
Mechanisms underlying the initial accumulation of tau pathology across the human brain are largely unknown. We examined whether baseline factors including age, amyloid-P (AP), and neural activity predicted longitudinal tau accumulation in temporal lobe regions that reflect distinct stages of tau pathogenesis. Seventy cognitively normal human older adults (77 +/- 6 years, 59% female) received two or more 18F-flortaucipir (FTP) and 11C-Pittsburgh Compound B (PiB) PET scans (mean follow-up, 2.5 +/- 1.1 years) to quantify tau and (AP). Linear mixed-effects models were used to calculate the slopes of FTP change in entorhinal cortex (EC), parahippocampal cortex (PHC), and inferior temporal gyrus (IT), and slopes of global PiB change. Thirty-seven participants underwent functional MilI to measure baseline activation. Older age predicted EC tau accumulation, and baseline EC tau levels predicted subsequent tau accumulation in EC and PHC. In IT, however, baseline EC tau interacted with AP to predict IT tau accumulation. Higher baseline local activation predicted tau accumulation within EC and PHC, and higher baseline hippocampal activation predicted EC tau accumulation. Our findings indicate that factors predicting tau accumulation vary as tau progresses through the temporal lobe. Older age is associated with initial tau accumulation in EC, while baseline EC tau and neural activity drive tau accumulation within medial temporal lobe. AP subsequently facilitates tau spread from medial to lateral temporal lobe. Our findings elucidate potential drivers of tau accumulation and spread in aging, which are critical for understanding Alzheimer's disease pathogenesis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据