Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
Neurobiol Aging. 2022 Aug;116:80-91. doi: 10.1016/j.neurobiolaging.2022.04.010. Epub 2022 Apr 22.
It is unclear whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration predict brain atrophy in cognitively healthy older adults, whether these associations can be explained by phosphorylated tau181 (p-tau) and the 42 amino acid form of amyloid-β (Aβ42) biomarkers, and which neural substrates may drive these associations. We addressed these questions in 2 samples of cognitively healthy older adults who underwent longitudinal structural MRI up to 7 years and had baseline CSF levels of heart-type fatty-acid binding protein (FABP3)=, total-tau, neurogranin, and neurofilament light (NFL) (n = 189, scans = 721). The results showed that NFL, total-tau, and FABP3 predicted entorhinal thinning and hippocampal atrophy. Brain atrophy was not moderated by Aβ42 and the associations between NFL and FABP3 with brain atrophy were independent of p-tau. The spatial pattern of cortical atrophy associated with the biomarkers overlapped with neurogenetic profiles associated with expression in the axonal (total-tau, NFL) and dendritic (neurogranin) components. CSF biomarkers of neurodegeneration are useful for predicting specific features of brain atrophy in older adults, independently of amyloid and tau pathology biomarkers.
目前尚不清楚神经退行性变的脑脊液（CSF）生物标志物是否可预测认知健康的老年人出现脑萎缩，这些相关性是否可以通过磷酸化 tau181（p-tau）和 42 个氨基酸形式的淀粉样β（Aβ42）生物标志物来解释，以及哪些神经基质可能驱动这些相关性。我们在 2 个认知健康的老年人样本中研究了这些问题，这些老年人接受了长达 7 年的纵向结构 MRI 检查，并在基线时检测到了心脏型脂肪酸结合蛋白（FABP3）=、总 tau、神经颗粒蛋白和神经丝轻链（NFL）的 CSF 水平（n=189，扫描次数=721）。结果表明，NFL、总 tau 和 FABP3 可预测内嗅皮层变薄和海马萎缩。脑萎缩不受 Aβ42 的调节，并且 NFL 和 FABP3 与脑萎缩之间的相关性与 p-tau 无关。与生物标志物相关的皮质萎缩的空间模式与与轴突（总 tau、NFL）和树突（神经颗粒蛋白）成分表达相关的神经遗传特征重叠。神经退行性变的 CSF 生物标志物可用于预测老年人脑萎缩的特定特征，与淀粉样蛋白和 tau 病理生物标志物无关。
