Association of In Vivo [18F]AV-1451 Tau PET Imaging Results With Cortical Atrophy and Symptoms in Typical and Atypical Alzheimer Disease

IMPORTANCE Previous postmortem studies have long demonstrated that neurofibrillary tangles made of hyperphosphorylated tau proteins are closely associated with Alzheimer disease clinical phenotype and neurodegeneration pattern. Validating these associations in vivo will lead to new diagnostic tools for Alzheimer disease and better understanding of its neurobiology. OBJECTIVE To examine whether topographical distribution and severity of hyperphosphorylated tau pathologic findings measured by fluorine 18-labeled AV-1451 ([F-18] AV-1451) positron emission tomographic (PET) imaging are linked with clinical phenotype and cortical atrophy in patients with Alzheimer disease. DESIGN, SETTING, AND PARTICIPANTS This observational case series, conducted from July 1, 2012, to July 30, 2015, in an outpatient referral center for patients with neurodegenerative diseases, included 6 patients: 3 with typical amnesic Alzheimer disease and 3 with atypical variants (posterior cortical atrophy, logopenic variant primary progressive aphasia, and corticobasal syndrome). Patients underwent [F-18]AV-1451 PET imaging to measure tau burden, carbon 11-labeled Pittsburgh Compound B ([C-11]PiB) PET imaging to measure amyloid burden, and structural magnetic resonance imaging to measure cortical thickness. Seventy-seven age-matched controls with normal cognitive function also underwent structural magnetic resonance imaging but not tau or amyloid PET imaging. MAIN OUTCOMES AND MEASURES Tau burden, amyloid burden, and cortical thickness. RESULTS In all 6 patients (3 women and 3 men; mean age 61.8 years), the underlying clinical phenotype was associated with the regional distribution of the [F-18]AV-1451 signal. Furthermore, within 68 cortical regions of interest measured from each patient, the magnitude of cortical atrophy was strongly correlated with the magnitude of [F-18]AV-1451 binding (3 patients with amnesic Alzheimer disease, r = -0.82; P < .001; r = -0.70; P < .001; r = -0.58; P < .001; and 3 patients with nonamnesic Alzheimer disease, r = -0.51; P < .001; r = -0.63; P < .001; r = -0.70; P < .001), but not of [C-11]PiB binding. CONCLUSIONS AND RELEVANCE These findings provide further in vivo evidence that distribution of the [18F] AV-1451 signal as seen on results of PET imaging is a valid marker of clinical symptoms and neurodegeneration. By localizing and quantifying hyperphosphorylated tau in vivo, results of tau PET imaging will likely serve as a key biomarker that links a specific type of molecular Alzheimer disease neuropathologic condition with clinically significant neurodegeneration, which will likely catalyze additional efforts to develop disease-modifying therapeutics.