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Yamamoto, Yumi; Hase, Yoshiki; Ihara, Masafumi; Khundakar, Ahmad; Roeber, Sigrun.; Duering, Marco and Kalaria, Raj N. (2021): Neuronal densities and vascular pathology in the hippocampal formation in CADASIL. In: Neurobiology of Aging, Vol. 97: pp. 33-40

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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 corticocortical and subcortical-cortical networks including the hippocampal formation. (C) 2020 The Authors. Published by ELSEVIER.

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