Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA.
Department of Biostatistics, University of California, Berkeley, CA, USA.
Cereb Cortex. 2019 May 1;29(5):1997-2009. doi: 10.1093/cercor/bhy078.
Tau is associated with hypometabolism in patients with Alzheimer's disease. In normal aging, the association between tau and glucose metabolism is not fully characterized. We used [18F] AV-1451, [18F] Fluorodeoxyglucose, and [11C] Pittsburgh Compound-B (PiB) PET to measure associations between tau and glucose metabolism in cognitively normal older adults (N = 49). Participants were divided into amyloid-negative (PiB-, n = 28) and amyloid-positive (PiB+, n = 21) groups to determine effects of amyloid-β. We assessed both local and across-brain regional tau-glucose metabolism associations separately in PiB-/PiB+ groups using correlation matrices and sparse canonical correlations. Relationships between tau and glucose metabolism differed by amyloid status, and were primarily spatially distinct. In PiB- subjects, tau was associated with broad regions of increased glucose metabolism. In PiB+ subjects, medial temporal lobe tau was associated with widespread hypometabolism, while tau outside of the medial temporal lobe was associated with decreased and increased glucose metabolism. We further found that regions with earlier tau spread were associated with stronger negative correlations with glucose metabolism. Our findings indicate that in normal aging, low levels of tau are associated with a phase of increased metabolism, while high levels of tau in the presence of amyloid-β are associated with hypometabolism at downstream sites.
tau 与阿尔茨海默病患者的代谢降低有关。在正常衰老过程中，tau 与葡萄糖代谢之间的关联尚未完全阐明。我们使用 [18F] AV-1451、[18F] 氟脱氧葡萄糖和 [11C] 匹兹堡化合物-B（PiB）PET 来测量认知正常的老年人（N = 49）中 tau 与葡萄糖代谢之间的关联。参与者分为淀粉样蛋白阴性（PiB-，n = 28）和淀粉样蛋白阳性（PiB+，n = 21）组，以确定淀粉样蛋白-β的影响。我们使用相关矩阵和稀疏典型相关，分别在 PiB-/PiB+组中评估局部和跨脑区域的 tau-葡萄糖代谢关联。tau 与葡萄糖代谢之间的关系因淀粉样蛋白状态而异，并且主要在空间上是不同的。在 PiB-受试者中，tau 与葡萄糖代谢增加的广泛区域相关。在 PiB+受试者中，内侧颞叶 tau 与广泛的代谢降低相关，而内侧颞叶以外的 tau 与葡萄糖代谢降低和升高相关。我们进一步发现，tau 早期扩散的区域与葡萄糖代谢的负相关更强。我们的研究结果表明，在正常衰老过程中，tau 水平较低与代谢增加的阶段有关，而在存在淀粉样蛋白-β的情况下，tau 水平较高与下游部位的代谢降低有关。
