Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary cerebral small vessel disease. Previous neuroimaging studies have suggested loss of hippocampal volume is a pathway for cognitive impairment in CADASIL. We used unbiased stereological methods to estimate SMI32-positive and total numbers and volumes of neurons in the hippocampal formation of 12 patients with CADASIL and similar age controls (young controls) and older controls. We found densities of SMI32-positive neurons in the entorhinal cortex, layer V, and cornu ammonis CA2 regions were reduced by 26%–50% in patients with CADASIL compared with young controls (p < 0.01), with a decreasing trend observed in older controls in the order of young controls> older controls ≥ CADASIL. These changes were not explained by any hippocampal infarct or vascular pathology or glial changes. Our results suggest notable loss of subsets of projection neurons within the hippocampal formation that may contribute to certain memory deficits in CADASIL, which is purely a vascular disease. It is likely that the severe arteriopathy leads to white matter damage which disconnects cortico-cortical and subcortical-cortical networks including the hippocampal formation.

中文翻译：

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CADASIL 海马结构中的神经元密度和血管病理学

伴有皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病 (CADASIL) 是遗传性脑小血管病的最常见形式。先前的神经影像学研究表明，海马体积的减少是 CADASIL 认知障碍的一个途径。我们使用无偏见的立体学方法来估计 12 名 CADASIL 患者和类似年龄的对照（年轻对照）和老年对照的海马结构中 SMI32 阳性和神经元的总数和体积。我们发现，与年轻对照相比，CADASIL 患者的内嗅皮层、V 层和角部 CA2 区域中 SMI32 阳性神经元的密度降低了 26%–50%（p < 0.01），在老年人中观察到降低趋势对照的顺序是年轻对照 > 年长对照 ≥ CADASIL。这些变化不能用任何海马梗塞或血管病理或神经胶质变化来解释。我们的研究结果表明，海马结构中投射神经元亚群的显着丢失可能导致 CADASIL 的某些记忆缺陷，这纯粹是一种血管疾病。严重的动脉病变很可能导致白质损伤，从而断开包括海马结构在内的皮质-皮质和皮质下-皮质网络。