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Capillary dysfunction in healthy elderly APOE ε4 carriers with raised brain Aβ deposition

Lookup NU author(s): Professor David BrooksORCiD

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


Abstract

© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. INTRODUCTION: Capillary dysfunction, characterized by disturbances in capillary blood flow distribution, might be an overlooked factor in the development of Alzheimer's disease (AD). This study investigated microvascular blood flow in preclinical and prodromal AD individuals. METHODS: Using dynamic susceptibility contrast magnetic resonance imaging and positron emission tomography, we examined alterations in microvascular circulation and levels of Aβ deposition in two independent cohorts of APOE ε4 carriers. RESULTS: Capillary dysfunction was elevated in both prodromal and preclinical AD individuals compared to age-matched controls. Additionally, the prodromal group exhibited higher levels of capillary dysfunction compared to the preclinical group. DISCUSSION: These findings suggest that capillary dysfunction can be detected at the preclinical stage of AD and indicates a worsening of capillary dysfunction throughout the AD continuum. Understanding the interaction between capillary dysfunction and Aβ could provide insights into the relationship between cardiovascular risk factors and the development of AD. Highlights: Alzheimer's disease (AD) is associated with disturbances in microvascular circulation. Capillary dysfunction can be detected in preclinical AD. As cognitive symptoms progress in prodromal AD, capillary dysfunction worsens. Capillary dysfunction may impede the clearance of beta-amyloid (Aβ). Capillary dysfunction might contribute to the development of AD.


Publication metadata

Author(s): Madsen LS, Kjeldsen PL, Ismail R, Parbo P, Østergaard L, Brooks DJ, Eskildsen SF

Publication type: Article

Publication status: Published

Journal: Alzheimer's and Dementia

Year: 2024

Volume: 20

Issue: 1

Pages: 459-471

Print publication date: 01/01/2024

Online publication date: 07/09/2023

Acceptance date: 13/08/2023

Date deposited: 14/08/2023

ISSN (print): 1552-5260

ISSN (electronic): 1552-5279

Publisher: John Wiley and Sons Inc.

URL: https://doi.org/10.1002/alz.13461

DOI: 10.1002/alz.13461

ePrints DOI: 10.57711/kxwq-0t17


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Funding

Funder referenceFunder name
0026167—Aarhus Research Center for Aging and Dementia
4004-00305
820636
Danish Council for Independent Research
European Union Horizon 2020
Lundbeck Foundation
The Danish Alzheimer's Association
R310-2018-3455

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