White matter integrity is associated with cerebrospinal fluid markers of Alzheimer's disease in normal adults

Brian T. Gold; Zude Zhu; Christopher A. Brown; Anders H. Andersen; Mary Jo LaDu; Leon Tai; Greg A. Jicha; Richard J. Kryscio; Steven Estus; Peter T. Nelson; Steve W. Scheff; Erin Abner; Frederick A. Schmitt; Linda J. Van Eldik; Charles D. Smith

doi:10.1016/j.neurobiolaging.2014.04.030

White matter integrity is associated with cerebrospinal fluid markers of Alzheimer's disease in normal adults

Brian T. Gold, Zude Zhu, Christopher A. Brown, Anders H. Andersen, Mary Jo LaDu, Leon Tai, Greg A. Jicha, Richard J. Kryscio, Steven Estus, Peter T. Nelson, Steve W. Scheff, Erin Abner, Frederick A. Schmitt, Linda J. Van Eldik, Charles D. Smith

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53 Scopus citations

Abstract

We explored whether white matter (WM) integrity in cognitively normal (CN) older adults is associated with cerebrospinal fluid (CSF) markers of Alzheimer's disease pathology. Twenty CN older adults underwent lumbar puncture and magnetic resonance imaging within a few days of each other. Analysis of diffusion tensor imaging data involved a priori region of interest and voxelwise approaches. The region of interest results revealed a positive correlation between CSF measures of amyloid-beta (Aβ₄₂ and Aβ₄₂/p-Tau₁₈₁) and WM integrity in the fornix, a relationship which persisted after controlling for hippocampal volume and fornix volume. Lower WM integrity in the same portion of the fornix was also associated with reduced performance on the Digit Symbol test. Subsequent exploratory voxelwise analyses indicated a positive correlation between CSF Aβ₄₂/p-Tau₁₈₁ and WM integrity in bilateral portions of the fornix, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and in the corpus callosum and left inferior longitudinal fasciculus. Our results link lower WM microstructural integrity in CN older adults with CSF biomarkers of Alzheimer's disease and suggest that this association in the fornix may be independent of volumetric measures.

Original language	English
Pages (from-to)	2263-2271
Number of pages	9
Journal	Neurobiology of Aging
Volume	35
Issue number	10
DOIs	https://doi.org/10.1016/j.neurobiolaging.2014.04.030
State	Published - Oct 2014

Bibliographical note

Funding Information:
This study was supported by the National Institute on Aging of the National Institutes of Health under award numbers ( P30 AG028383 , P01 AG030128 , R01 AG033036 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of these granting agencies. The authors thank Beverly Meacham for her assistance in scanning participants. Most of all, they wish to thank the dedicated volunteers at the Sanders-Brown Center on Aging for their participation in this research.

Keywords

CSF
DTI
Normal older adults
Preclinical AD
White matter

ASJC Scopus subject areas

General Neuroscience
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2014.04.030

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Gold, B. T., Zhu, Z., Brown, C. A., Andersen, A. H., LaDu, M. J., Tai, L., Jicha, G. A., Kryscio, R. J., Estus, S., Nelson, P. T., Scheff, S. W., Abner, E., Schmitt, F. A., Van Eldik, L. J., & Smith, C. D. (2014). White matter integrity is associated with cerebrospinal fluid markers of Alzheimer's disease in normal adults. Neurobiology of Aging, 35(10), 2263-2271. https://doi.org/10.1016/j.neurobiolaging.2014.04.030

@article{4aebfe95d044453788bce368d9b01bd2,

title = "White matter integrity is associated with cerebrospinal fluid markers of Alzheimer's disease in normal adults",

abstract = "We explored whether white matter (WM) integrity in cognitively normal (CN) older adults is associated with cerebrospinal fluid (CSF) markers of Alzheimer's disease pathology. Twenty CN older adults underwent lumbar puncture and magnetic resonance imaging within a few days of each other. Analysis of diffusion tensor imaging data involved a priori region of interest and voxelwise approaches. The region of interest results revealed a positive correlation between CSF measures of amyloid-beta (Aβ42 and Aβ42/p-Tau181) and WM integrity in the fornix, a relationship which persisted after controlling for hippocampal volume and fornix volume. Lower WM integrity in the same portion of the fornix was also associated with reduced performance on the Digit Symbol test. Subsequent exploratory voxelwise analyses indicated a positive correlation between CSF Aβ42/p-Tau181 and WM integrity in bilateral portions of the fornix, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and in the corpus callosum and left inferior longitudinal fasciculus. Our results link lower WM microstructural integrity in CN older adults with CSF biomarkers of Alzheimer's disease and suggest that this association in the fornix may be independent of volumetric measures.",

keywords = "CSF, DTI, Normal older adults, Preclinical AD, White matter",

author = "Gold, {Brian T.} and Zude Zhu and Brown, {Christopher A.} and Andersen, {Anders H.} and LaDu, {Mary Jo} and Leon Tai and Jicha, {Greg A.} and Kryscio, {Richard J.} and Steven Estus and Nelson, {Peter T.} and Scheff, {Steve W.} and Erin Abner and Schmitt, {Frederick A.} and {Van Eldik}, {Linda J.} and Smith, {Charles D.}",

note = "Funding Information: This study was supported by the National Institute on Aging of the National Institutes of Health under award numbers ( P30 AG028383 , P01 AG030128 , R01 AG033036 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of these granting agencies. The authors thank Beverly Meacham for her assistance in scanning participants. Most of all, they wish to thank the dedicated volunteers at the Sanders-Brown Center on Aging for their participation in this research.",

year = "2014",

month = oct,

doi = "10.1016/j.neurobiolaging.2014.04.030",

language = "English",

volume = "35",

pages = "2263--2271",

number = "10",

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Gold, BT, Zhu, Z, Brown, CA, Andersen, AH, LaDu, MJ, Tai, L, Jicha, GA , Kryscio, RJ , Estus, S , Nelson, PT, Scheff, SW, Abner, E , Schmitt, FA , Van Eldik, LJ & Smith, CD 2014, 'White matter integrity is associated with cerebrospinal fluid markers of Alzheimer's disease in normal adults', Neurobiology of Aging, vol. 35, no. 10, pp. 2263-2271. https://doi.org/10.1016/j.neurobiolaging.2014.04.030

TY - JOUR

T1 - White matter integrity is associated with cerebrospinal fluid markers of Alzheimer's disease in normal adults

AU - Gold, Brian T.

AU - Zhu, Zude

AU - Brown, Christopher A.

AU - Andersen, Anders H.

AU - LaDu, Mary Jo

AU - Tai, Leon

AU - Jicha, Greg A.

AU - Kryscio, Richard J.

AU - Estus, Steven

AU - Nelson, Peter T.

AU - Scheff, Steve W.

AU - Abner, Erin

AU - Schmitt, Frederick A.

AU - Van Eldik, Linda J.

AU - Smith, Charles D.

N1 - Funding Information: This study was supported by the National Institute on Aging of the National Institutes of Health under award numbers ( P30 AG028383 , P01 AG030128 , R01 AG033036 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of these granting agencies. The authors thank Beverly Meacham for her assistance in scanning participants. Most of all, they wish to thank the dedicated volunteers at the Sanders-Brown Center on Aging for their participation in this research.

PY - 2014/10

Y1 - 2014/10

N2 - We explored whether white matter (WM) integrity in cognitively normal (CN) older adults is associated with cerebrospinal fluid (CSF) markers of Alzheimer's disease pathology. Twenty CN older adults underwent lumbar puncture and magnetic resonance imaging within a few days of each other. Analysis of diffusion tensor imaging data involved a priori region of interest and voxelwise approaches. The region of interest results revealed a positive correlation between CSF measures of amyloid-beta (Aβ42 and Aβ42/p-Tau181) and WM integrity in the fornix, a relationship which persisted after controlling for hippocampal volume and fornix volume. Lower WM integrity in the same portion of the fornix was also associated with reduced performance on the Digit Symbol test. Subsequent exploratory voxelwise analyses indicated a positive correlation between CSF Aβ42/p-Tau181 and WM integrity in bilateral portions of the fornix, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and in the corpus callosum and left inferior longitudinal fasciculus. Our results link lower WM microstructural integrity in CN older adults with CSF biomarkers of Alzheimer's disease and suggest that this association in the fornix may be independent of volumetric measures.

AB - We explored whether white matter (WM) integrity in cognitively normal (CN) older adults is associated with cerebrospinal fluid (CSF) markers of Alzheimer's disease pathology. Twenty CN older adults underwent lumbar puncture and magnetic resonance imaging within a few days of each other. Analysis of diffusion tensor imaging data involved a priori region of interest and voxelwise approaches. The region of interest results revealed a positive correlation between CSF measures of amyloid-beta (Aβ42 and Aβ42/p-Tau181) and WM integrity in the fornix, a relationship which persisted after controlling for hippocampal volume and fornix volume. Lower WM integrity in the same portion of the fornix was also associated with reduced performance on the Digit Symbol test. Subsequent exploratory voxelwise analyses indicated a positive correlation between CSF Aβ42/p-Tau181 and WM integrity in bilateral portions of the fornix, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and in the corpus callosum and left inferior longitudinal fasciculus. Our results link lower WM microstructural integrity in CN older adults with CSF biomarkers of Alzheimer's disease and suggest that this association in the fornix may be independent of volumetric measures.

KW - CSF

KW - DTI

KW - Normal older adults

KW - Preclinical AD

KW - White matter

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DO - 10.1016/j.neurobiolaging.2014.04.030

M3 - Article

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AN - SCOPUS:84903816441

SN - 0197-4580

VL - 35

SP - 2263

EP - 2271

JO - Neurobiology of Aging

JF - Neurobiology of Aging

IS - 10

ER -

White matter integrity is associated with cerebrospinal fluid markers of Alzheimer's disease in normal adults

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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