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

Abstract

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 paper 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 differedmore » 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. Finally, 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.« less

Authors:
 [1];  [2];  [3];  [2];  [2];  [4];  [5];  [5]
  1. Univ. of California, Berkeley, CA (United States); German Center for Neurodegenerative Diseases, Magdeburg (Germany)
  2. Univ. of California, Berkeley, CA (United States)
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  4. Univ. of California, San Francisco, CA (United States)
  5. Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, San Francisco, CA (United States)
Publication Date:
Research Org.:
Univ. of California, San Francisco, CA (United States); Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE; National Inst. of Health (NIH) (United States)
OSTI Identifier:
1393249
DOE Contract Number:  
AC02-05CH11231; R01-AG045611; R01AG034570; P50-AG023501; P01-AG1972403
Resource Type:
Journal Article
Journal Name:
NeuroImage
Additional Journal Information:
Journal Volume: 157; Journal ID: ISSN 1053-8119
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; tau; β-amyloid; positron emission tomography; AV-1451; biomarker; Alzheimer's disease

Citation Formats

Maass, Anne, Landau, Susan, Baker, Suzanne L., Horng, Andy, Lockhart, Samuel N., La Joie, Renaud, Rabinovici, Gil D., and Jagust, William J. Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease. United States: N. p., 2017. Web. doi:10.1016/j.neuroimage.2017.05.058.
Maass, Anne, Landau, Susan, Baker, Suzanne L., Horng, Andy, Lockhart, Samuel N., La Joie, Renaud, Rabinovici, Gil D., & Jagust, William J. Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease. United States. doi:10.1016/j.neuroimage.2017.05.058.
Maass, Anne, Landau, Susan, Baker, Suzanne L., Horng, Andy, Lockhart, Samuel N., La Joie, Renaud, Rabinovici, Gil D., and Jagust, William J. Sat . "Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease". United States. doi:10.1016/j.neuroimage.2017.05.058.
@article{osti_1393249,
title = {Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease},
author = {Maass, Anne and Landau, Susan and Baker, Suzanne L. and Horng, Andy and Lockhart, Samuel N. and La Joie, Renaud and Rabinovici, Gil D. and Jagust, William J.},
abstractNote = {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 paper 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. Finally, 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.},
doi = {10.1016/j.neuroimage.2017.05.058},
journal = {NeuroImage},
issn = {1053-8119},
number = ,
volume = 157,
place = {United States},
year = {2017},
month = {6}
}