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

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 [F-18]-AV-1451 positron emission tomography (PET) imaging to stage AD and assess the associations among beta-amyloid (A beta), 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 [F-18]-AV-1451 in the hippocampus and a priori-defined AD cortical signature regions, cerebrospinal fluid A beta 42, hippocampal volume, and AD signature cortical thickness. RESULTS Of the 59 participants, 38 (64%) were male; mean (SD) age was 74 (6) years. The [F-18]-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 [F-18]-AV-1451 SUVR cutoff value of 1.19 (sensitivity, 100%; specificity, 86%) from AD cortical signature regions best separated cerebrospinal fluid A beta 42-positive (A beta+) AD from cerebrospinal fluid A beta 42-negative (A beta-) CN participants. This same cutoff also divided A beta+ CN participants into low vs high tau groups. Moreover, the presence of A beta+ was associated with an elevated [F-18]-AV-1451 SUVR in AD cortical signature regions (A beta+ participants: mean [SD], 1.3 [0.3]; A beta-participants: 1.1 [0.1]; F = 4.3, P = .04) but not in the hippocampus. The presence of A beta+ alone was not related to hippocampal volume or AD signature cortical thickness. An elevated [F-18]-AV-1451 SUVR was associated with volumetric loss in both the hippocampus and AD cortical signature regions. The observed [F-18]-AV-1451 SUVR volumetric association was modified by A beta status in the hippocampus but not in AD cortical signature regions. An inverse association between hippocampal [F-18]-AV-1451 SUVR and volume was seen in A beta+ participants (R-2 = 0.55; P < .001) but not A beta-(R-2 = 0; P = .97) participants. CONCLUSIONS AND RELEVANCE Use of [F-18]-AV-1451 has a potential for staging of the preclinical and clinical phases of AD. beta-Amyloid interacts with hippocampal and cortical tauopathy to affect neurodegeneration. In the absence of A beta, hippocampal tau deposition may be insufficient for the neurodegenerative process that leads to AD.