PET Imaging of Tau Pathology and Relationship to Amyloid, Longitudinal MRI, and Cognitive Change in Down Syndrome: Results from the Down Syndrome Biomarker Initiative (DSBI)

Article type: Research Article

Authors: Rafii, Michael S.^{a; b; *} | Lukic, Ana S.^c | Andrews, Randolph D.^c | Brewer, James^b | Rissman, Robert A.^{b; g} | Strother, Stephen C.^{c; d} | Wernick, Miles N.^{c; e} | Pennington, Craig^c | Mobley, William C.^b | Ness, Seth^f | Matthews, Dawn C.^c | for the Down Syndrome Biomarker Initiative and the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Alzheimer’s Therapeutic Research Institute (ATRI), Keck School of Medicine, University of Southern California, San Diego, USA | [b] Department of Neurosciences, University of California San Diego School of Medicine, La Jolla, CA, USA | [c] ADM Diagnostics, Northbrook, IL, USA | [d] Rotman Research Institute, Baycrest, Toronto, ON, CA, USA | [e] Medical Imaging Research Center, Illinois Institute of Technology, Chicago, IL, USA | [f] Janssen Research and Development LLC, Raritan, NJ, USA | [g] Veterans Administration Medical Center, La Jolla, CA, USA

Correspondence: [*] Correspondence to: Michael S. Rafii, MD, PhD, Alzheimer’s Therapeutic Research Institute (ATRI), Keck School of Medicine, University of Southern California, 9860 Mesa Rim Road, San Diego, CA 92121, USA. Tel.: +1 858 964 0638; E-mail: [email protected].

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:Adults with Down syndrome (DS) represent an enriched population for the development of Alzheimer’s disease (AD), which could aid the study of therapeutic interventions, and in turn, could benefit from discoveries made in other AD populations. Objectives:1) Understand the relationship between tau pathology and age, amyloid deposition, neurodegeneration (MRI and FDG PET), and cognitive and functional performance; 2) detect and differentiate AD-specific changes from DS-specific brain changes in longitudinal MRI. Methods:Twelve non-demented adults, ages 30 to 60, with DS were enrolled in the Down Syndrome Biomarker Initiative (DSBI), a 3-year, observational, cohort study to demonstrate the feasibility of conducting AD intervention/prevention trials in adults with DS. We collected imaging data with 18F-AV-1451 tau PET, AV-45 amyloid PET, FDG PET, and volumetric MRI, as well as cognitive and functional measures and additional laboratory measures. Results:All amyloid negative subjects imaged were tau-negative. Among the amyloid positive subjects, three had tau in regions associated with Braak stage VI, two at stage V, and one at stage II. Amyloid and tau burden correlated with age. The MRI analysis produced two distinct volumetric patterns. The first differentiated DS from normal (NL) and AD, did not correlate with age or amyloid, and was longitudinally stable. The second pattern reflected AD-like atrophy and differentiated NL from AD. Tau PET and MRI atrophy correlated with several cognitive and functional measures. Conclusions:Tau accumulation is associated with amyloid positivity and age, as well as with progressive neurodegeneration measurable using FDG and MRI. Tau correlates with cognitive decline, as do AD-specific hypometabolism and atrophy.

Keywords: Alzheimer’s disease, biomarkers, dementia, Down syndrome, Tau PET, volumetric MRI

DOI: 10.3233/JAD-170390

Journal: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 439-450, 2017