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

Anne Maass; Susan Landau; Suzanne L Baker; Andy Horng; Samuel N Lockhart; Renaud La Joie; Gil D Rabinovici; William J Jagust; Alzheimer's Disease Neuroimaging Initiative

doi:10.1016/j.neuroimage.2017.05.058

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

Neuroimage. 2017 Aug 15:157:448-463. doi: 10.1016/j.neuroimage.2017.05.058. Epub 2017 Jun 3.

Authors

Anne Maass¹, Susan Landau², Suzanne L Baker³, Andy Horng⁴, Samuel N Lockhart⁵, Renaud La Joie⁶, Gil D Rabinovici⁷, William J Jagust⁸; Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, United States; German Center for Neurodegenerative Diseases, Magdeburg, Germany. Electronic address: anne.maass@dzne.de.
² Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, United States. Electronic address: slandau@berkeley.edu.
³ Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Lab, Berkeley, CA, United States. Electronic address: slbaker@lbl.gov.
⁴ Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, United States. Electronic address: andyhorng1@gmail.com.
⁵ Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, United States. Electronic address: snl@berkeley.edu.
⁶ Memory and Aging Center, University of California San Francisco, San Francisco, CA, United States. Electronic address: Renaud.LaJoie@ucsf.edu.
⁷ Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, United States; Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Lab, Berkeley, CA, United States; Memory and Aging Center, University of California San Francisco, San Francisco, CA, United States. Electronic address: Gil.Rabinovici@ucsf.edu.
⁸ Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, United States; Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Lab, Berkeley, CA, United States; Memory and Aging Center, University of California San Francisco, San Francisco, CA, United States. Electronic address: jagust@berkeley.edu.

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 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.

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

Publication types

Comparative Study

MeSH terms

Adult
Age of Onset
Aged
Aged, 80 and over
Aging / metabolism*
Alzheimer Disease / diagnostic imaging
Alzheimer Disease / metabolism*
Alzheimer Disease / pathology
Alzheimer Disease / physiopathology
Amyloid beta-Peptides / metabolism*
Carbolines
Cognitive Dysfunction / diagnostic imaging
Cognitive Dysfunction / metabolism*
Cognitive Dysfunction / pathology
Cognitive Dysfunction / physiopathology
Cohort Studies
Female
Humans
Male
Middle Aged
Neocortex / diagnostic imaging
Neocortex / metabolism*
Positron-Emission Tomography / methods*
Severity of Illness Index*
Young Adult
tau Proteins / metabolism*

Substances

Amyloid beta-Peptides
Carbolines
tau Proteins
7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

Abstract

Publication types

MeSH terms

Substances

Grants and funding