TY  - JOUR
AU  - Maaß, Anne
AU  - Landau, Susan
AU  - Baker, Suzanne L
AU  - Horng, Andy
AU  - Lockhart, Samuel N
AU  - La Joie, Renaud
AU  - Rabinovici, Gil D
AU  - Jagust, William J
AU  - Initiative, Alzheimer's Disease Neuroimaging
TI  - Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease.
JO  - NeuroImage
VL  - 157
SN  - 1053-8119
CY  - Orlando, Fla.
PB  - Academic Press
M1  - DZNE-2020-05825
SP  - 448-463
PY  - 2017
AB  - 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.
KW  - Adult
KW  - Age of Onset
KW  - Aged
KW  - Aged, 80 and over
KW  - Aging: metabolism
KW  - Alzheimer Disease: diagnostic imaging
KW  - Alzheimer Disease: metabolism
KW  - Alzheimer Disease: pathology
KW  - Alzheimer Disease: physiopathology
KW  - Amyloid beta-Peptides: metabolism
KW  - Carbolines
KW  - Cognitive Dysfunction: diagnostic imaging
KW  - Cognitive Dysfunction: metabolism
KW  - Cognitive Dysfunction: pathology
KW  - Cognitive Dysfunction: physiopathology
KW  - Cohort Studies
KW  - Female
KW  - Humans
KW  - Male
KW  - Middle Aged
KW  - Neocortex: diagnostic imaging
KW  - Neocortex: metabolism
KW  - Positron-Emission Tomography: methods
KW  - Severity of Illness Index
KW  - Young Adult
KW  - tau Proteins: metabolism
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Carbolines (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
KW  - 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:28587897
C2  - pmc:PMC5814575
DO  - DOI:10.1016/j.neuroimage.2017.05.058
UR  - https://pub.dzne.de/record/139503
ER  -