Plasma Tau Association with Brain Atrophy in Mild Cognitive Impairment and Alzheimer’s Disease
Article type: Research Article
Authors: Deters, Kacie D.a; b; c | Risacher, Shannon L.a; b | Kim, Sungeuna; b; d | Nho, Kwangsika; b | West, John D.a | Blennow, Kaje | Zetterberg, Henrike; f | Shaw, Leslie M.g | Trojanowski, John Q.g | Weiner, Michael W.h | Saykin, Andrew J.a; b; c; * | for the Alzheimer Disease Neuroimaging Initiative1
Affiliations: [a] Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA | [b] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA | [c] Program in Medical Neuroscience, Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA | [d] Department of Electrical and Computer Engineering, State University of New York, Oswego, NY, USA | [e] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden | [f] Department of Molecular Neuroscience, University College London Institute of Neurology, London, UK | [g] Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA | [h] Department of Radiology, Medicine, and Psychiatry, University of California San Francisco, San Francisco, CA, USA
Correspondence: [*] Correspondence to: Dr. Andrew J. Saykin, Department of Radiology and Imaging Sciences, Indiana University School of Medicine,355W. 16th St., Suite 4100, Indianapolis, Indiana 46202, USA. Tel.: +1 317 963 7501; Fax: +1 317 963 7547; E-mail: asaykin@iupui.edu.
Note: [1] Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
Abstract: Background: Peripheral (plasma) and central (cerebrospinal fluid, CSF) measures of tau are higher in Alzheimer’s disease (AD) relative to prodromal stages and controls. While elevated CSF tau concentrations have been shown to be associated with lower grey matter density (GMD) in AD-specific regions, this correlation has yet to be examined for plasma in a large study. Objective: Determine the neuroanatomical correlates of plasma tau using voxel-based analysis. Methods: Cross-sectional data for 508 ADNI participants were collected for clinical, plasma total-tau (t-tau), CSF amyloid (Aβ42) and tau, and MRI variables. The relationship between plasma tau and GMD and between CSF t-tau and GMD were assessed on a voxel-by-voxel basis using regression models. Age, sex, APOE ɛ4 status, diagnosis, and total intracranial volume were used as covariates where appropriate. Participants were defined as amyloid positive (Aβ+) if CSF Aβ42 was <192 pg/mL. Results: Plasma tau was negatively correlated with GMD in the medial temporal lobe (MTL), precuneus, thalamus, and striatum. The associations with thalamus and striatum were independent of diagnosis. A negative correlation also existed between plasma tau and GMD in Aβ+ participants in the MTL, precuneus, and frontal lobe. When compared to CSF t-tau, plasma tau showed a notably different associated brain atrophy pattern, with only small overlapping regions in the fusiform gyrus. Conclusion: Plasma tau may serve as a non-specific marker for neurodegeneration but is still relevant to AD considering low GMD was associated with plasma tau in Aβ+ participants and not Aβ–participants.
Keywords: Alzheimer disease, magnetic resonance imaging, mild cognitive impairment, plasma, tau protein
DOI: 10.3233/JAD-161114
Journal: Journal of Alzheimer's Disease, vol. 58, no. 4, pp. 1245-1254, 2017
