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. 2017 Apr 1;74(4):427-436.
doi: 10.1001/jamaneurol.2016.5755.

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

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Free PMC article

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

Chenjie Xia et al. JAMA Neurol. .
Free PMC article

Abstract

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 ([18F]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 [18F]AV-1451 PET imaging to measure tau burden, carbon 11-labeled Pittsburgh Compound B ([11C]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 [18F]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 [18F]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 [11C]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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Hyman reported receiving personal fees from Siemens, Calico, ISIS Pharma, Eli Lilly, Neurophage Pharmaceuticals, Pfizer, Biogen, Genentech, Sanofi, AbbVie, and Novartis; receving grants from Siemens, Biogen Idec, BMS, AZTherapies, Acumen, Prothena, Fidelity Biosciences, Spark, and Intellect; and having a family member employed by Novartis. Dr Vasdev reported holding patent number WO 2014194169 A1 20141204, “Radiosynthesis of Tau Radio-Pharmaceuticals” (2014). Dr Johnson reported receiving personal fees from Piramal, Novartis, Siemens, Lilly/Avid, Janssen, AZTherapies, Roche, Genentech, GE Healthcare, Biogen Idec, and ISIS Pharma; receiving grants from Lilly/Avid, Merck, Janssen, Eisai, Biogen Idec, the National Institutes of Health, and the Michael J. Fox Foundation. Dr Dickerson reported receiving personal fees from Merck, Forum, and Ionis Pharma. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Regional Distributions of Tau, Atrophy, and Amyloid in Patients With Typical Alzheimer Disease (AD)
The thresholds selected represent the 50th (minimum) and 95th (maximum) percentile values for each imaging modality for each patient. [11C]PiB indicates carbon 11–labeled Pittsburgh Compound B; DVR, distribution volume ratio; [18F]AV-1451, fluorine 18–labeled AV-1451; and SUVR, standardized uptake value ratio.
Figure 2.
Figure 2.. Regional Distributions of Tau, Atrophy, and Amyloid in Patients With Atypical Alzheimer Disease
The thresholds selected represent the 50th (minimum) and 95th (maximum) percentile values for each imaging modality for each patient. CBS indicates corticobasal syndrome; [11C]PiB, carbon 11–labeled Pittsburgh Compound B; DVR, distribution volume ratio; [18F]AV-1451, fluorine 18–labeled AV-1451; lvPPA, logopenic variant primary progressive aphasia; PCA, posterior cortical atrophy; and SUVR, standardized uptake value ratio.
Figure 3.
Figure 3.. Correlations Between Cortical Atrophy and Tau vs Amyloid in Patients With Typical Alzheimer Disease (AD)
Shapes representing cortical regions of interest: left frontal, amber circles; left temporal, green circles; left parietal, maroon circles; left occipital, blue circles; right frontal, amber triangles; right temporal, green triangles; right parietal, maroon triangles; and right occipital, blue triangles. [11C]PiB indicates carbon 11–labeled Pittsburgh Compound B; [18F]AV-1451, fluorine 18–labeled AV-1451. aP < .001.
Figure 4.
Figure 4.. Correlations Between Cortical Atrophy and Tau vs Amyloid in Patients With Atypical Alzheimer Disease
Shapes representing cortical regions of interest: left frontal, amber circles; left temporal, green circles; left parietal, maroon circles; left occipital, blue circles; right frontal, amber triangles; right temporal, green triangles; right parietal, maroon triangles; and right occipital, blue triangles. CBS indicates corticobasal syndrome; [11C]PiB, carbon 11–labeled Pittsburgh Compound B; [18F]AV-1451, fluorine 18–labeled AV-1451; lvPPA, logopenic variant primary progressive aphasia; and PCA, posterior cortical atrophy. aP < .001.

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