Cerebral amyloid burden is associated with white matter hyperintensity location in specific posterior white matter regions

Nick A. Weaver, Thomas Doeven, Frederik Barkhof, J. Matthijs Biesbroek, Onno N. Groeneveld, Hugo J. Kuijf, Niels D. Prins, Philip Scheltens, Charlotte E. Teunissen, Wiesje M. van der Flier, Geert Jan Biessels, TRACE-VCI study group

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

White matter hyperintensities (WMHs) are a common manifestation of cerebral small vessel disease. WMHs are also frequently observed in patients with familial and sporadic Alzheimer's disease, often with a particular posterior predominance. Whether amyloid and tau pathologies are linked to WMH occurrence is still debated. We examined whether cerebral amyloid and tau burden, reflected in cerebrospinal fluid amyloid-beta 1-42 (Aβ-42) and phosphorylated tau (p-tau), are related to WMH location in a cohort of 517 memory clinic patients. Two lesion mapping techniques were performed: voxel-based analyses and region of interest-based linear regression. Voxelwise associations were found between lower Aβ-42 and parieto-occipital periventricular WMHs. Regression analyses demonstrated that lower Aβ-42 correlated with larger WMH volumes in the splenium of the corpus callosum and posterior thalamic radiation, also after controlling for markers of vascular disease. P-tau was not consistently related to WMH occurrence. Our findings indicate that cerebral amyloid burden is associated with WMHs located in specific posterior white matter regions, possibly reflecting region-specific effects of amyloid pathology on the white matter.
Original languageEnglish
JournalNeurobiology of Aging
DOIs
Publication statusAccepted/In press - 2019

Cite this

@article{6cfbb1ee0dc94a249ed849c6cb472b46,
title = "Cerebral amyloid burden is associated with white matter hyperintensity location in specific posterior white matter regions",
abstract = "White matter hyperintensities (WMHs) are a common manifestation of cerebral small vessel disease. WMHs are also frequently observed in patients with familial and sporadic Alzheimer's disease, often with a particular posterior predominance. Whether amyloid and tau pathologies are linked to WMH occurrence is still debated. We examined whether cerebral amyloid and tau burden, reflected in cerebrospinal fluid amyloid-beta 1-42 (Aβ-42) and phosphorylated tau (p-tau), are related to WMH location in a cohort of 517 memory clinic patients. Two lesion mapping techniques were performed: voxel-based analyses and region of interest-based linear regression. Voxelwise associations were found between lower Aβ-42 and parieto-occipital periventricular WMHs. Regression analyses demonstrated that lower Aβ-42 correlated with larger WMH volumes in the splenium of the corpus callosum and posterior thalamic radiation, also after controlling for markers of vascular disease. P-tau was not consistently related to WMH occurrence. Our findings indicate that cerebral amyloid burden is associated with WMHs located in specific posterior white matter regions, possibly reflecting region-specific effects of amyloid pathology on the white matter.",
author = "Weaver, {Nick A.} and Thomas Doeven and Frederik Barkhof and Biesbroek, {J. Matthijs} and Groeneveld, {Onno N.} and Kuijf, {Hugo J.} and Prins, {Niels D.} and Philip Scheltens and Teunissen, {Charlotte E.} and {van der Flier}, {Wiesje M.} and Biessels, {Geert Jan} and {TRACE-VCI study group}",
year = "2019",
doi = "10.1016/j.neurobiolaging.2019.08.001",
language = "English",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",

}

Cerebral amyloid burden is associated with white matter hyperintensity location in specific posterior white matter regions. / Weaver, Nick A.; Doeven, Thomas; Barkhof, Frederik; Biesbroek, J. Matthijs; Groeneveld, Onno N.; Kuijf, Hugo J.; Prins, Niels D.; Scheltens, Philip; Teunissen, Charlotte E.; van der Flier, Wiesje M.; Biessels, Geert Jan; TRACE-VCI study group.

In: Neurobiology of Aging, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Cerebral amyloid burden is associated with white matter hyperintensity location in specific posterior white matter regions

AU - Weaver, Nick A.

AU - Doeven, Thomas

AU - Barkhof, Frederik

AU - Biesbroek, J. Matthijs

AU - Groeneveld, Onno N.

AU - Kuijf, Hugo J.

AU - Prins, Niels D.

AU - Scheltens, Philip

AU - Teunissen, Charlotte E.

AU - van der Flier, Wiesje M.

AU - Biessels, Geert Jan

AU - TRACE-VCI study group

PY - 2019

Y1 - 2019

N2 - White matter hyperintensities (WMHs) are a common manifestation of cerebral small vessel disease. WMHs are also frequently observed in patients with familial and sporadic Alzheimer's disease, often with a particular posterior predominance. Whether amyloid and tau pathologies are linked to WMH occurrence is still debated. We examined whether cerebral amyloid and tau burden, reflected in cerebrospinal fluid amyloid-beta 1-42 (Aβ-42) and phosphorylated tau (p-tau), are related to WMH location in a cohort of 517 memory clinic patients. Two lesion mapping techniques were performed: voxel-based analyses and region of interest-based linear regression. Voxelwise associations were found between lower Aβ-42 and parieto-occipital periventricular WMHs. Regression analyses demonstrated that lower Aβ-42 correlated with larger WMH volumes in the splenium of the corpus callosum and posterior thalamic radiation, also after controlling for markers of vascular disease. P-tau was not consistently related to WMH occurrence. Our findings indicate that cerebral amyloid burden is associated with WMHs located in specific posterior white matter regions, possibly reflecting region-specific effects of amyloid pathology on the white matter.

AB - White matter hyperintensities (WMHs) are a common manifestation of cerebral small vessel disease. WMHs are also frequently observed in patients with familial and sporadic Alzheimer's disease, often with a particular posterior predominance. Whether amyloid and tau pathologies are linked to WMH occurrence is still debated. We examined whether cerebral amyloid and tau burden, reflected in cerebrospinal fluid amyloid-beta 1-42 (Aβ-42) and phosphorylated tau (p-tau), are related to WMH location in a cohort of 517 memory clinic patients. Two lesion mapping techniques were performed: voxel-based analyses and region of interest-based linear regression. Voxelwise associations were found between lower Aβ-42 and parieto-occipital periventricular WMHs. Regression analyses demonstrated that lower Aβ-42 correlated with larger WMH volumes in the splenium of the corpus callosum and posterior thalamic radiation, also after controlling for markers of vascular disease. P-tau was not consistently related to WMH occurrence. Our findings indicate that cerebral amyloid burden is associated with WMHs located in specific posterior white matter regions, possibly reflecting region-specific effects of amyloid pathology on the white matter.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31500909

U2 - 10.1016/j.neurobiolaging.2019.08.001

DO - 10.1016/j.neurobiolaging.2019.08.001

M3 - Article

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

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