Water exchange rate across the blood-brain barrier is associated with CSF amyloid-β 42 in healthy older adults

Brian T. Gold; Xingfeng Shao; Tiffany L. Sudduth; Gregory A. Jicha; Donna M. Wilcock; Elayna R. Seago; Danny J.J. Wang

doi:10.1002/alz.12357

Water exchange rate across the blood-brain barrier is associated with CSF amyloid-β 42 in healthy older adults

Brian T. Gold, Xingfeng Shao, Tiffany L. Sudduth, Gregory A. Jicha, Donna M. Wilcock, Elayna R. Seago, Danny J.J. Wang

Research output: Contribution to journal › Article › peer-review

54 Scopus citations

Abstract

Introduction: We tested if water exchange across the blood-brain barrier (BBB), estimated with a noninvasive magnetic resonance imaging (MRI) technique, is associated with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and neuropsychological function. Methods: Forty cognitively normal older adults (67–86 years old) were scanned with diffusion-prepared, arterial spin labeling (DP-ASL), which estimates water exchange rate across the BBB (k_w). Participants also underwent CSF draw and neuropsychological testing. Multiple linear regression models were run with k_w as a predictor of CSF concentrations and neuropsychological scores. Results: In multiple brain regions, BBB k_w was positively associated with CSF amyloid beta (Aβ)42 concentration levels. BBB k_w was only moderately associated with neuropsychological performance. Discussion: Our results suggest that low water exchange rate across the BBB is associated with low CSF Aβ42 concentration. These findings suggest that k_w may be a promising noninvasive indicator of BBB Aβ clearance functions, a possibility which should be further tested in future research.

Original language	English
Pages (from-to)	2020-2029
Number of pages	10
Journal	Alzheimer's and Dementia
Volume	17
Issue number	12
DOIs	https://doi.org/10.1002/alz.12357
State	Published - Dec 2021

Bibliographical note

Publisher Copyright:
© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association

Funding

The authors thank Dr. Shoshana Bardach for help with participant recruitment and Dr. David Powell, Beverly Meacham and Eric Foreman for assisting/conducting the MRI scans. This work was supported by the National Institutes of Health (grant numbers NIA R01AG055449, NIA P30 AG028383 NIGMS S10 OD023573, UH3\u2010NS100614, R01\u2010NS114382, and R01\u2010EB028297). The content is solely the responsibility of the authors and does not necessarily represent the official views of these granting agencies. The authors thank Dr. Shoshana Bardach for help with participant recruitment and Dr. David Powell, Beverly Meacham and Eric Foreman for assisting/conducting the MRI scans. This work was supported by the National Institutes of Health (grant numbers NIA R01AG055449, NIA P30 AG028383 NIGMS S10 OD023573, UH3-NS100614, R01-NS114382, and R01-EB028297). The content is solely the responsibility of the authors and does not necessarily represent the official views of these granting agencies.

Funders	Funder number
National Institutes of Health (NIH)
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council	R01NS114382, UH3NS100614
National Institute of Biomedical Imaging and Bioengineering	R01EB028297
NIH Office of the Director	S10OD023573
National Institute on Aging	R01AG055449, P30 AG028383 NIGMS S10 OD023573, P30AG072946

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/alz.12357

Cite this

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title = "Water exchange rate across the blood-brain barrier is associated with CSF amyloid-β 42 in healthy older adults",

abstract = "Introduction: We tested if water exchange across the blood-brain barrier (BBB), estimated with a noninvasive magnetic resonance imaging (MRI) technique, is associated with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and neuropsychological function. Methods: Forty cognitively normal older adults (67–86 years old) were scanned with diffusion-prepared, arterial spin labeling (DP-ASL), which estimates water exchange rate across the BBB (kw). Participants also underwent CSF draw and neuropsychological testing. Multiple linear regression models were run with kw as a predictor of CSF concentrations and neuropsychological scores. Results: In multiple brain regions, BBB kw was positively associated with CSF amyloid beta (Aβ)42 concentration levels. BBB kw was only moderately associated with neuropsychological performance. Discussion: Our results suggest that low water exchange rate across the BBB is associated with low CSF Aβ42 concentration. These findings suggest that kw may be a promising noninvasive indicator of BBB Aβ clearance functions, a possibility which should be further tested in future research.",

author = "Gold, \{Brian T.\} and Xingfeng Shao and Sudduth, \{Tiffany L.\} and Jicha, \{Gregory A.\} and Wilcock, \{Donna M.\} and Seago, \{Elayna R.\} and Wang, \{Danny J.J.\}",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors. Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association",

year = "2021",

month = dec,

doi = "10.1002/alz.12357",

language = "English",

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AU - Jicha, Gregory A.

AU - Wilcock, Donna M.

AU - Seago, Elayna R.

AU - Wang, Danny J.J.

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N2 - Introduction: We tested if water exchange across the blood-brain barrier (BBB), estimated with a noninvasive magnetic resonance imaging (MRI) technique, is associated with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and neuropsychological function. Methods: Forty cognitively normal older adults (67–86 years old) were scanned with diffusion-prepared, arterial spin labeling (DP-ASL), which estimates water exchange rate across the BBB (kw). Participants also underwent CSF draw and neuropsychological testing. Multiple linear regression models were run with kw as a predictor of CSF concentrations and neuropsychological scores. Results: In multiple brain regions, BBB kw was positively associated with CSF amyloid beta (Aβ)42 concentration levels. BBB kw was only moderately associated with neuropsychological performance. Discussion: Our results suggest that low water exchange rate across the BBB is associated with low CSF Aβ42 concentration. These findings suggest that kw may be a promising noninvasive indicator of BBB Aβ clearance functions, a possibility which should be further tested in future research.

AB - Introduction: We tested if water exchange across the blood-brain barrier (BBB), estimated with a noninvasive magnetic resonance imaging (MRI) technique, is associated with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and neuropsychological function. Methods: Forty cognitively normal older adults (67–86 years old) were scanned with diffusion-prepared, arterial spin labeling (DP-ASL), which estimates water exchange rate across the BBB (kw). Participants also underwent CSF draw and neuropsychological testing. Multiple linear regression models were run with kw as a predictor of CSF concentrations and neuropsychological scores. Results: In multiple brain regions, BBB kw was positively associated with CSF amyloid beta (Aβ)42 concentration levels. BBB kw was only moderately associated with neuropsychological performance. Discussion: Our results suggest that low water exchange rate across the BBB is associated with low CSF Aβ42 concentration. These findings suggest that kw may be a promising noninvasive indicator of BBB Aβ clearance functions, a possibility which should be further tested in future research.

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Water exchange rate across the blood-brain barrier is associated with CSF amyloid-β 42 in healthy older adults

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

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