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Capillary function progressively deteriorates in prodromal Alzheimer’s disease: A longitudinal MRI perfusion study

Lookup NU author(s): Professor David BrooksORCiD

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Abstract

Cardiovascular risk factors are associated with the development of Alzheimer’s disease (AD), and increasing evidence suggests that cerebral microvascular dysfunction plays a vital role in the disease progression. Using magnetic resonance imaging, we investigated the two-year changes of the cerebral microvascular blood flow in 11 mild cognitively impaired (MCI) patients with prodromal AD compared to 12 MCI patients without evidence of AD and 10 cognitively intact age-matched controls. The pAD-MCI patients displayed widespread deterioration in microvascular cerebral perfusion associated with capillary dysfunction. No such changes were observed in the other two groups, suggesting that the dysfunction in capillary perfusion is linked to the AD pathophysiology. The observed capillary dysfunction may limit local oxygenation in AD leading to downstream bamyloid aggregation, tau hyperphosphorylation, neuroinflammation and neuronal dysfunction. The findings are in agreement with the capillary dysfunction hypothesis of AD, suggesting that increasing heterogeneity of capillary blood flow is a primary pathological event in AD.

Publication metadata

Author(s): Madsen LS, Nielsen RB, Parbo P, Ismail R, Mikkelsen IK, Gottrup H, Østergaard L, Brooks DJ, Eskildsen SF

Publication type: Article

Publication status: Published

Journal: Aging Brain

Year: 2022

Volume: 2

Online publication date: 19/02/2022

Acceptance date: 04/02/2022

Date deposited: 13/10/2022

ISSN (electronic): 2589-9589

Publisher: Elsevier Inc.

URL: https://doi.org/10.1016/j.nbas.2022.100035

DOI: 10.1016/j.nbas.2022.100035

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