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Capillary dysfunction correlates with cortical amyloid load in early Alzheimer's disease

Lookup NU author(s): Professor David BrooksORCiD

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Abstract

Alzheimer’s disease is characterised by plaques of β-amyloid in the cerebral cortex, however, the mechanisms leading to β-amyloid accumulation and downstream neurodegeneration remain elusive. Alterations in cerebral perfusion is increasingly considered to play a crucial role in Alzheimer’s disease and together with accumulated β-amyloid, deficiencies in the brain microvascular circulation may result in local hypoxia. Here, we studied the correlation between β-amyloid load and cerebral perfusion in individuals with mild cognitive impairment (MCI) and elevated levels of cortical β-amyloid. Using dynamic susceptibility contrast MRI and PET, we evaluated cerebral perfusion and β-amyloid levels of 32 MCI patients. A subgroup of 19 MCI patients showed evidence of elevated β-amyloid burden and was used to evaluate the correlation between perfusion parameters and β-amyloid load. Raised β-amyloid levels correlated with decreased microvascular blood flow and increased heterogeneity of microvascular blood flow in frontal and temporal areas (p<0.01). These results indicate a close connection between levels of β-amyloid deposition and and brain microvascular perfusion in early Alzheimer’s disease. A vicious cycle may be established where β-amyloid load and deficiencies in brain perfusion may reinforce each other.

Publication metadata

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

Publication type: Article

Publication status: Published

Journal: Neurobiology of Aging

Year: 2023

Volume: 123

Pages: 1-9

Print publication date: 01/03/2023

Online publication date: 16/12/2022

Acceptance date: 12/12/2022

Date deposited: 16/12/2022

ISSN (print): 0197-4580

ISSN (electronic): 1558-1497

Publisher: Elsevier Inc.

URL: https://doi.org/10.1016/j.neurobiolaging.2022.12.006

DOI: 10.1016/j.neurobiolaging.2022.12.006

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