Relationship Between CSF Biomarkers of Alzheimer's Disease and Rates of Regional Cortical Thinning in ADNI Data

Issue title: Imaging the Alzheimer Brain

Guest editors: J. Wesson Ashford, Allyson Rosen, Maheen Adamson, Peter Bayley, Osama Sabri, Ansgar Furst, Sandra E. Black and Michael Weiner

Article type: Research Article

Authors: Tosun, Duygu^{a; *} | Schuff, Norbert^{a; b} | Shaw, Leslie M.^c | Trojanowski, John Q.^c | Weiner, Michael W.^{a; b} | the Alzheimer's Disease NeuroImaging Initiative

Affiliations: [a] Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, San Francisco, CA, USA | [b] Department of Radiology, University of California, San Francisco, CA, USA | [c] Department of Pathology and Laboratory Medicine, Medicine at the Hospital of the University of Pennsylvania, Philadelphia, PA, USA

Correspondence: [*] Correspondence to: Duygu Tosun, Ph.D, Center for Imaging Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, 4150 Clement St, Blg 13, 114M, San Francisco, CA, 94121, USA. Tel.: +1 415 221 4810, ext 4800, Fax: +1 415 668 2864; E-mail: duygu.tosun@ucsf.edu.

Note: [1] Data used in the preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu ADNI). 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. Complete listing of ADNI investigators is available at http://www.loni.ucla.edu/ADNI/Collaboration/ADNI_Manuscript_Citations.pdf.

Abstract: Previously it was reported that Alzheimer's disease (AD) patients have reduced amyloid (Aβ1-42) and elevated total tau (t-tau) and phosphorylated tau (p-tau181p) in the cerebro-spinal fluid (CSF), suggesting that these same measures could be used to detect early AD pathology in healthy elderly (CN) and mild cognitive impairment (MCI). In this study, we tested the hypothesis that there would be an association among rates of regional brain atrophy, the CSF biomarkers Aβ1-42, t-tau, and p-tau181p and ApoE ε4 status, and that the pattern of this association would be diagnosis specific. Our findings primarily showed that lower CSF Aβ1-42 and higher tau concentrations were associated with increased rates of regional brain tissue loss and the patterns varied across the clinical groups. Taken together, these findings demonstrate that CSF biomarker concentrations are associated with the characteristic patterns of structural brain changes in CN and MCI that resemble to a large extent the pathology seen in AD. Therefore, the finding of faster progression of brain atrophy in the presence of lower Aβ1-42 levels and higher p-tau levels supports the hypothesis that CSF Aβ1-42 and tau are measures of early AD pathology. Moreover, the relationship among CSF biomarkers, ApoE ε4 status, and brain atrophy rates are regionally varying, supporting the view that the genetic predisposition of the brain to amyloid and tau mediated pathology is regional and disease stage specific.

Keywords: MRI, Alzheimer's disease, cerebrospinal fluid, biomarkers, cortical thickness, atrophy, ApoE

DOI: 10.3233/JAD-2011-0006

Journal: Journal of Alzheimer's Disease, vol. 26, no. s3, pp. 77-90, 2011