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

Lasse Stensvig Madsen; Peter Parbo; Rola Ismail; Hanne Gottrup; Leif Østergaard; David J Brooks; Simon Fristed Eskildsen

doi:10.1016/j.neurobiolaging.2022.12.006

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

Lasse Stensvig Madsen^*, Peter Parbo, Rola Ismail, Hanne Gottrup, Leif Østergaard, David J Brooks, Simon Fristed Eskildsen

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

16 Citationer (Scopus)

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Abstract

Alterations in cerebral perfusion is increasingly considered to play a crucial role in Alzheimer’s disease (AD) and together with accumulated amyloid-β, deficiencies in the brain microvascular circulation may result in local hypoxia. Here, we studied alterations in cerebral circulation and the correlation between amyloid-β load and cerebral perfusion in prodromal AD (pAD). Using dynamic susceptibility contrast MRI and PET, we evaluated cerebral perfusion and amyloid-β levels in 19 individuals with mild cognitive impairment (MCI) and high amyloid-β load (pAD-MCI), 13 MCI individuals without AD pathology and 21 healthy controls. The pAD-MCI group showed significantly lower microvascular blood flow and significantly higher heterogeneity of microvascular blood transit times (p < 0.01) compared with the other 2 groups. Additionally, in the pAD-MCI group raised amyloid-β 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 amyloid-β deposition and brain microvascular perfusion in pAD. A vicious cycle may be established where amyloid-β load and deficiencies in brain perfusion may reinforce each other.

Originalsprog	Engelsk
Tidsskrift	Neurobiology of Aging
Vol/bind	123
Sider (fra-til)	1-9
Antal sider	9
ISSN	0197-4580
DOI	https://doi.org/10.1016/j.neurobiolaging.2022.12.006
Status	Udgivet - mar. 2023

Emneord

Alzheimer’s disease
Capillary
Amyloid-β
Mild cognitive impairment
Perfusion MRI
PiB PET
Blood flow

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10.1016/j.neurobiolaging.2022.12.006Licens: CC BY

1-s2.0-S0197458022002603-mainForlagets udgivne version, 1,95 MBLicens: CC BY

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title = "Capillary dysfunction correlates with cortical amyloid load in early Alzheimer's disease",

abstract = "Alterations in cerebral perfusion is increasingly considered to play a crucial role in Alzheimer{\textquoteright}s disease (AD) and together with accumulated amyloid-β, deficiencies in the brain microvascular circulation may result in local hypoxia. Here, we studied alterations in cerebral circulation and the correlation between amyloid-β load and cerebral perfusion in prodromal AD (pAD). Using dynamic susceptibility contrast MRI and PET, we evaluated cerebral perfusion and amyloid-β levels in 19 individuals with mild cognitive impairment (MCI) and high amyloid-β load (pAD-MCI), 13 MCI individuals without AD pathology and 21 healthy controls. The pAD-MCI group showed significantly lower microvascular blood flow and significantly higher heterogeneity of microvascular blood transit times (p < 0.01) compared with the other 2 groups. Additionally, in the pAD-MCI group raised amyloid-β 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 amyloid-β deposition and brain microvascular perfusion in pAD. A vicious cycle may be established where amyloid-β load and deficiencies in brain perfusion may reinforce each other.",

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author = "Madsen, {Lasse Stensvig} and Peter Parbo and Rola Ismail and Hanne Gottrup and Leif {\O}stergaard and Brooks, {David J} and Eskildsen, {Simon Fristed}",

year = "2023",

month = mar,

doi = "10.1016/j.neurobiolaging.2022.12.006",

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AU - Madsen, Lasse Stensvig

AU - Parbo, Peter

AU - Ismail, Rola

AU - Gottrup, Hanne

AU - Østergaard, Leif

AU - Brooks, David J

AU - Eskildsen, Simon Fristed

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N2 - Alterations in cerebral perfusion is increasingly considered to play a crucial role in Alzheimer’s disease (AD) and together with accumulated amyloid-β, deficiencies in the brain microvascular circulation may result in local hypoxia. Here, we studied alterations in cerebral circulation and the correlation between amyloid-β load and cerebral perfusion in prodromal AD (pAD). Using dynamic susceptibility contrast MRI and PET, we evaluated cerebral perfusion and amyloid-β levels in 19 individuals with mild cognitive impairment (MCI) and high amyloid-β load (pAD-MCI), 13 MCI individuals without AD pathology and 21 healthy controls. The pAD-MCI group showed significantly lower microvascular blood flow and significantly higher heterogeneity of microvascular blood transit times (p < 0.01) compared with the other 2 groups. Additionally, in the pAD-MCI group raised amyloid-β 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 amyloid-β deposition and brain microvascular perfusion in pAD. A vicious cycle may be established where amyloid-β load and deficiencies in brain perfusion may reinforce each other.

AB - Alterations in cerebral perfusion is increasingly considered to play a crucial role in Alzheimer’s disease (AD) and together with accumulated amyloid-β, deficiencies in the brain microvascular circulation may result in local hypoxia. Here, we studied alterations in cerebral circulation and the correlation between amyloid-β load and cerebral perfusion in prodromal AD (pAD). Using dynamic susceptibility contrast MRI and PET, we evaluated cerebral perfusion and amyloid-β levels in 19 individuals with mild cognitive impairment (MCI) and high amyloid-β load (pAD-MCI), 13 MCI individuals without AD pathology and 21 healthy controls. The pAD-MCI group showed significantly lower microvascular blood flow and significantly higher heterogeneity of microvascular blood transit times (p < 0.01) compared with the other 2 groups. Additionally, in the pAD-MCI group raised amyloid-β 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 amyloid-β deposition and brain microvascular perfusion in pAD. A vicious cycle may be established where amyloid-β load and deficiencies in brain perfusion may reinforce each other.

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KW - Amyloid-β

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KW - Perfusion MRI

KW - PiB PET

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