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CSF T-Tau/Aβ42 predicts white matter microstructure in healthy adults at risk for Alzheimer's disease

Bendlin, BB; Carlsson, CM; Johnson, SC; Zetterberg, H; Blennow, K; Willette, AA; Okonkwo, OC; ... Sager, MA; + view all (2012) CSF T-Tau/Aβ42 predicts white matter microstructure in healthy adults at risk for Alzheimer's disease. PLoS One , 7 (6) , Article e37720. 10.1371/journal.pone.0037720. Green open access

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Abstract

Cerebrospinal fluid (CSF) biomarkers T-Tau and Aβ(42) are linked with Alzheimer's disease (AD), yet little is known about the relationship between CSF biomarkers and structural brain alteration in healthy adults. In this study we examined the extent to which AD biomarkers measured in CSF predict brain microstructure indexed by diffusion tensor imaging (DTI) and volume indexed by T1-weighted imaging. Forty-three middle-aged adults with parental family history of AD received baseline lumbar puncture and MRI approximately 3.5 years later. Voxel-wise image analysis methods were used to test whether baseline CSF Aβ(42), total tau (T-Tau), phosphorylated tau (P-Tau) and neurofilament light protein predicted brain microstructure as indexed by DTI and gray matter volume indexed by T1-weighted imaging. T-Tau and T-Tau/Aβ(42) were widely correlated with indices of brain microstructure (mean, axial, and radial diffusivity), notably in white matter regions adjacent to gray matter structures affected in the earliest stages of AD. None of the CSF biomarkers were related to gray matter volume. Elevated P-Tau and P-Tau/Aβ(42) levels were associated with lower recognition performance on the Rey Auditory Verbal Learning Test. Overall, the results suggest that CSF biomarkers are related to brain microstructure in healthy adults with elevated risk of developing AD. Furthermore, the results clearly suggest that early pathological changes in AD can be detected with DTI and occur not only in cortex, but also in white matter.

Type: Article
Title: CSF T-Tau/Aβ42 predicts white matter microstructure in healthy adults at risk for Alzheimer's disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0037720
Publisher version: http://dx.doi.org/10.1371/journal.pone.0037720
Language: English
Additional information: © 2012 Bendlin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3368882
Keywords: Adult, Alzheimer Disease, Amyloid beta-Peptides, Analysis of Variance, Biological Markers, Diffusion Tensor Imaging, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Myelin Sheath, Neuropsychological Tests, Peptide Fragments, Phosphorylation, Recognition (Psychology), Wisconsin, tau Proteins
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/1411976
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