Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, H3A 2B4, QC, Canada.
Department of Physics, Concordia University, Montreal, H4B 1R6, QC, Canada.
Nat Commun. 2024 Jun 3;15(1):4706. doi: 10.1038/s41467-024-48490-z.
The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer's disease (AD). They project broadly throughout the brain's white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns between IdC and white matter microstructure in 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for AD. IdC integrity related to 1) whole-brain neurite density, and 2) neurite orientation dispersion in white matter tracts known to be affected early in AD. Pattern 2 was associated with CSF concentration of phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both patterns more strongly than non-carriers. IdC microstructure variation is reflected in white matter, particularly in AD-affected tracts, highlighting an early mechanism of pathological development.
神经调节亚皮质核位于等树突核心（IdC）内，是阿尔茨海默病（AD）tau 病的最早部位。它们广泛投射到大脑的白质中。我们研究了 IdC 微观结构与全脑白质微观结构之间的关系，以更好地了解 AD 的早期神经病理学变化。使用多参数定量磁共振成像，我们在 133 名认知正常的老年人（年龄 67.9±5.3 岁）中观察到两个与 AD 家族风险相关的 IdC 和白质微观结构之间的协方差模式。IdC 完整性与 1）全脑神经丝密度，以及 2）AD 早期受影响的白质束中的神经丝取向分散有关。模式 2 与 CSF 中磷酸化 tau 的浓度相关，表明具有 AD 特异性。载脂蛋白 E4 携带者比非携带者更强烈地表达这两种模式。IdC 微观结构的变化反映在白质中，特别是在受 AD 影响的束中，突出了病理发展的早期机制。
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