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Gray matter hypoperfusion is a late pathological event in the course of Alzheimer's disease

Ahmadi, Khazar LU ; Pereira, Joana B LU ; Berron, David LU ; Vogel, Jacob LU ; Ingala, Silvia ; Strandberg, Olof T LU ; Janelidze, Shorena LU ; Barkhof, Frederik ; Pfeuffer, Josef and Knutsson, Linda LU orcid , et al. (2023) In Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 43(4). p.565-580
Abstract

Several studies have shown decreased cerebral blood flow (CBF) in Alzheimer's disease (AD). However, the role of hypoperfusion in the disease pathogenesis remains unclear. Combining arterial spin labeling MRI, PET, and CSF biomarkers, we investigated the associations between gray matter (GM)-CBF and the key mechanisms in AD including amyloid-β (Aβ) and tau pathology, synaptic and axonal degeneration. Further, we applied a disease progression modeling to characterize the temporal sequence of different AD biomarkers. Lower perfusion was observed in temporo-occipito-parietal cortex in the Aβ-positive cognitively impaired compared to both Aβ-negative and Aβ-positive cognitively unimpaired individuals. In participants along the AD spectrum,... (More)

Several studies have shown decreased cerebral blood flow (CBF) in Alzheimer's disease (AD). However, the role of hypoperfusion in the disease pathogenesis remains unclear. Combining arterial spin labeling MRI, PET, and CSF biomarkers, we investigated the associations between gray matter (GM)-CBF and the key mechanisms in AD including amyloid-β (Aβ) and tau pathology, synaptic and axonal degeneration. Further, we applied a disease progression modeling to characterize the temporal sequence of different AD biomarkers. Lower perfusion was observed in temporo-occipito-parietal cortex in the Aβ-positive cognitively impaired compared to both Aβ-negative and Aβ-positive cognitively unimpaired individuals. In participants along the AD spectrum, GM-CBF was associated with tau, synaptic and axonal dysfunction, but not Aβ in similar cortical regions. Axonal degeneration was further associated with hypoperfusion in cognitively unimpaired individuals. Disease progression modeling revealed that GM-CBF disruption Followed the abnormality of biomarkers of Aβ, tau and brain atrophy. These findings indicate that tau tangles and neurodegeneration are more closely connected with GM-CBF changes than Aβ pathology. Although subjected to the sensitivity of the employed neuroimaging techniques and the modeling approach, these findings suggest that hypoperfusion might not be an early event associated with the build-up of Aβ in preclinical phase of AD.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
volume
43
issue
4
pages
565 - 580
publisher
Nature Publishing Group
external identifiers
  • scopus:85142634560
  • pmid:36412244
ISSN
1559-7016
DOI
10.1177/0271678X221141139
language
English
LU publication?
yes
id
aeb596bb-80c8-4a98-821a-3ac43ac15a6c
date added to LUP
2022-11-26 16:54:10
date last changed
2024-06-13 13:22:52
@article{aeb596bb-80c8-4a98-821a-3ac43ac15a6c,
  abstract     = {{<p>Several studies have shown decreased cerebral blood flow (CBF) in Alzheimer's disease (AD). However, the role of hypoperfusion in the disease pathogenesis remains unclear. Combining arterial spin labeling MRI, PET, and CSF biomarkers, we investigated the associations between gray matter (GM)-CBF and the key mechanisms in AD including amyloid-β (Aβ) and tau pathology, synaptic and axonal degeneration. Further, we applied a disease progression modeling to characterize the temporal sequence of different AD biomarkers. Lower perfusion was observed in temporo-occipito-parietal cortex in the Aβ-positive cognitively impaired compared to both Aβ-negative and Aβ-positive cognitively unimpaired individuals. In participants along the AD spectrum, GM-CBF was associated with tau, synaptic and axonal dysfunction, but not Aβ in similar cortical regions. Axonal degeneration was further associated with hypoperfusion in cognitively unimpaired individuals. Disease progression modeling revealed that GM-CBF disruption Followed the abnormality of biomarkers of Aβ, tau and brain atrophy. These findings indicate that tau tangles and neurodegeneration are more closely connected with GM-CBF changes than Aβ pathology. Although subjected to the sensitivity of the employed neuroimaging techniques and the modeling approach, these findings suggest that hypoperfusion might not be an early event associated with the build-up of Aβ in preclinical phase of AD.</p>}},
  author       = {{Ahmadi, Khazar and Pereira, Joana B and Berron, David and Vogel, Jacob and Ingala, Silvia and Strandberg, Olof T and Janelidze, Shorena and Barkhof, Frederik and Pfeuffer, Josef and Knutsson, Linda and van Westen, Danielle and Palmqvist, Sebastian and Mutsaerts, Henk Jmm and Hansson, Oskar}},
  issn         = {{1559-7016}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{565--580}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism}},
  title        = {{Gray matter hypoperfusion is a late pathological event in the course of Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1177/0271678X221141139}},
  doi          = {{10.1177/0271678X221141139}},
  volume       = {{43}},
  year         = {{2023}},
}