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Neuronal densities and vascular pathology in the hippocampal formation in CADASIL

Lookup NU author(s): Yumi Yamamoto, Dr Yoshiki HaseORCiD, Dr Masafumi Ihara, Dr Ahmad Khundakar, Professor Raj KalariaORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2020 The Authors. 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.


Publication metadata

Author(s): Yamamoto Y, Hase Y, Ihara M, Khundakar A, Roeber S, Duering M, Kalaria RN

Publication type: Article

Publication status: Published

Journal: Neurobiology of Aging

Year: 2021

Volume: 97

Pages: 33-40

Print publication date: 01/01/2021

Online publication date: 01/10/2020

Acceptance date: 21/09/2020

Date deposited: 10/11/2020

ISSN (print): 0197-4580

ISSN (electronic): 1558-1497

Publisher: Elsevier Inc.

URL: https://doi.org/10.1016/j.neurobiolaging.2020.09.016

DOI: 10.1016/j.neurobiolaging.2020.09.016


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Funding

Funder referenceFunder name
BBSRC
EPSRC
ESRC
G050024
G0400074
MRC

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