Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease

NeuroImage

Suzanne L. Baker¹  Susan Landau²  Renaud La Joie³  Gil D. Rabinovici³  Anne Maass³  Andy Horng³  William J. Jagust⁴  Samuel N. Lockhart⁵ 

[1] Correspondence to: Jagust Laboratory, Helen Wills Neuroscience Institute, 132 Barker Hall, MC 3190, University of California, Berkeley, CA 94720-3190, USA.;German Center for Neurodegenerative Diseases, Magdeburg, Germany;Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, United States;Memory and Aging Center, University of California San Francisco, San Francisco, CA, United States;Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Lab, Berkeley, CA, United States;

关键词: Tau;    β-amyloid;    Positron emission tomography;    AV-1451;    Biomarker;    Alzheimer's disease;   

DOI  :  

来源: DOAJ

【 摘 要 】

The recent development of tau-specific positron emission tomography (PET) tracers enables in vivo quantification of regional tau pathology, one of the key lesions in Alzheimer's disease (AD). Tau PET imaging may become a useful biomarker for clinical diagnosis and tracking of disease progression but there is no consensus yet on how tau PET signal is best quantified. The goal of the current study was to evaluate multiple whole-brain and region-specific approaches to detect clinically relevant tau PET signal. Two independent cohorts of cognitively normal adults and amyloid-positive (Aβ+) patients with mild cognitive impairment (MCI) or AD-dementia underwent [18F]AV-1451 PET. Methods for tau tracer quantification included: (i) in vivo Braak staging, (ii) regional uptake in Braak composite regions, (iii) several whole-brain measures of tracer uptake, (iv) regional uptake in AD-vulnerable voxels, and (v) uptake in a priori defined regions. Receiver operating curves characterized accuracy in distinguishing Aβ- controls from AD/MCI patients and yielded tau positivity cutoffs. Clinical relevance of tau PET measures was assessed by regressions against cognition and MR imaging measures. Key tracer uptake patterns were identified by a factor analysis and voxel-wise contrasts. Braak staging, global and region-specific tau measures yielded similar diagnostic accuracies, which differed between cohorts. While all tau measures were related to amyloid and global cognition, memory and hippocampal/entorhinal volume/thickness were associated with regional tracer retention in the medial temporal lobe. Key regions of tau accumulation included medial temporal and inferior/middle temporal regions, retrosplenial cortex, and banks of the superior temporal sulcus. Our data indicate that whole-brain tau PET measures might be adequate biomarkers to detect AD-related tau pathology. However, regional measures covering AD-vulnerable regions may increase sensitivity to early tau PET signal, atrophy and memory decline.

【 授权许可】

Unknown