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JAMA Neurol. 2016 Sep 1;73(9):1070-7. doi: 10.1001/jamaneurol.2016.2078.

Evaluation of Tau Imaging in Staging Alzheimer Disease and Revealing Interactions Between β-Amyloid and Tauopathy.

Author information

1
Department of Neurology, Washington University, St Louis, Missouri2The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St Louis, Missouri.
2
The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St Louis, Missouri3Department of Radiology, Washington University, St Louis, Missouri.
3
Department of Radiology, Washington University, St Louis, Missouri.
4
Department of Radiology, University of Alabama, Birmingham.
5
Department of Neurology, Washington University, St Louis, Missouri2The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St Louis, Missouri5The Hope Center for Neurological Disorders at Washington University, St Louis, Missouri.
6
Department of Neurology, Washington University, St Louis, Missouri2The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St Louis, Missouri3Department of Radiology, Washington University, St Louis, Missouri5The Hope Center for Neurological Disorders at Washington University, St Louis, Missouri.

Abstract

IMPORTANCE:

In vivo tau imaging may become a diagnostic marker for Alzheimer disease (AD) and provides insights into the pathophysiology of AD.

OBJECTIVE:

To evaluate the usefulness of [18F]-AV-1451 positron emission tomography (PET) imaging to stage AD and assess the associations among β-amyloid (Aβ), tau, and volume loss.

DESIGN, SETTING, AND PARTICIPANTS:

An imaging study conducted at Knight Alzheimer Disease Research Center at Washington University in St Louis, Missouri. A total of 59 participants who were cognitively normal (CN) (Clinical Dementia Rating [CDR] score, 0) or had AD dementia (CDR score, >0) were included.

MAIN OUTCOMES AND MEASURES:

Standardized uptake value ratio (SUVR) of [18F]-AV-1451 in the hippocampus and a priori-defined AD cortical signature regions, cerebrospinal fluid Aβ42, hippocampal volume, and AD signature cortical thickness.

RESULTS:

Of the 59 participants, 38 (64%) were male; mean (SD) age was 74 (6) years. The [18F]-AV-1451 SUVR in the hippocampus and AD cortical signature regions distinguished AD from CN participants (area under the receiver operating characteristic curve range [95% CI], 0.89 [0.73-1.00] to 0.98 [0.92-1.00]). An [18F]-AV-1451 SUVR cutoff value of 1.19 (sensitivity, 100%; specificity, 86%) from AD cortical signature regions best separated cerebrospinal fluid Aβ42-positive (Aβ+) AD from cerebrospinal fluid Aβ42-negative (Aβ-) CN participants. This same cutoff also divided Aβ+ CN participants into low vs high tau groups. Moreover, the presence of Aβ+ was associated with an elevated [18F]-AV-1451 SUVR in AD cortical signature regions (Aβ+ participants: mean [SD], 1.3 [0.3]; Aβ- participants: 1.1 [0.1]; F = 4.3, P = .04) but not in the hippocampus. The presence of Aβ+ alone was not related to hippocampal volume or AD signature cortical thickness. An elevated [18F]-AV-1451 SUVR was associated with volumetric loss in both the hippocampus and AD cortical signature regions. The observed [18F]-AV-1451 SUVR volumetric association was modified by Aβ status in the hippocampus but not in AD cortical signature regions. An inverse association between hippocampal [18F]-AV-1451 SUVR and volume was seen in Aβ+ participants (R2 = 0.55; P < .001) but not Aβ- (R2 = 0; P = .97) participants.

CONCLUSIONS AND RELEVANCE:

Use of [18F]-AV-1451 has a potential for staging of the preclinical and clinical phases of AD. β-Amyloid interacts with hippocampal and cortical tauopathy to affect neurodegeneration. In the absence of Aβ, hippocampal tau deposition may be insufficient for the neurodegenerative process that leads to AD.

Comment in

PMID:
27454922
PMCID:
PMC5237382
DOI:
10.1001/jamaneurol.2016.2078
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Disclosures: Dr Fagan is a member of the scientific advisory boards of IBL International and Roche and is a consultant for AbbVie, Novartis, and DiamiR. Drs Benzinger and Morris and are currently participating in a clinical trial of antidementia drugs: A4 (The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease) trial. Dr Benzinger also participates in the Dominantly Inherited Alzheimer Network Trials Unit and in clinical trials sponsored by Eli Lilly/Avid Radiopharmaceuticals. Dr Morris has served as a consultant for Lilly USA and Takeda Pharmaceuticals. Drs Benzinger and Morris receive research support from Eli Lilly/Avid Radiopharmaceuticals. Dr McConathy has served as a consultant for Eli Lilly/Avid Radiopharmaceuticals, GE Healthcare, and Siemens Healthcare. No other disclosures were reported.

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