Neuronal densities and vascular pathology in the hippocampal formation in CADASIL

Yumi Yamamoto, Yoshiki Hase, Masafumi Ihara, Ahmad Khundakar, Sigrun Roeber, Marco Duering, Raj N. Kalaria

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Abstract

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.

Original languageEnglish
Pages (from-to)33-40
Number of pages8
JournalNeurobiology of Aging
Volume97
Early online date1 Oct 2020
DOIs
Publication statusPublished - Jan 2021

Bibliographical note

Funding Information:
This work is enabled by funding from the Overseas Research Studentship Awards. R.K.'s work was supported by grants from the UK Medical Research Council (MRC, G0500247 ), Newcastle Centre for Brain Ageing and Vitality (BBSRC, EPSRC, ESRC and MRC, LLHW). The NBTR is funded by a grant from the UK MRC (G0400074) with further support from the Newcastle NIHR Biomedical Research Centre in Ageing and Age Related Diseases award to the Newcastle upon Tyne Hospitals NHS Foundation Trust, and a grant from the Alzheimer's Society and ART as part of the Brains for Dementia Research Project and BrainNet II Europe, Germany.

Publisher Copyright:
© 2020 The Authors

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

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