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

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 ([ 18 F]AV-1451) positron emission tomographic (PET) imaging are linked with clinical phenotype and cortical atrophy in patients with Alzheimer disease. DESIGN, SETTING, AND PARTICIPANTSThis 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 [ 18 F]AV-1451 PET imaging to measure tau burden, carbon 11-labeled Pittsburgh Compound B ([ 11 C]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 MEASURESTau burden, amyloid burden, and cortical thickness. RESULTSIn 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 [ 18 F]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 [ 18 F]AV-1451 binding (3 patients with amnesic Alzheimer disease, r = -0.82; P < .

CSF neurogranin or tau distinguish typical and atypical Alzheimer disease

“…Previous studies have shown that individuals presenting with the visual variant of AD, PCA, have proportionately more regional atrophy, cortical thinning and tau deposition in the occipitoparietal regions than hippocampi and other medial temporal structures compared to those with typical memory led AD 24, 25, 26. Our imaging findings are broadly in keeping with these, with the PCA patients having larger hippocampal and small parietal lobe volumes than patients with typical AD.…”

Regional Distribution, Asymmetry, and Clinical Correlates of Tau Uptake on [18F]AV-1451 PET in Atypical Alzheimer’s Disease

“…These tau-PET findings of hemispheric asymmetry are particularly valuable because autopsy studies are typically performed with only one hemisphere, and hence do not allow the assessment of asymmetry in tau pathology. The fact that we looked at tau in both hemispheres, and that it seems to match asymmetry in grey matter atrophy and FDG hypometabolism, supports an association between tau deposition and cerebral atrophy [1–3, 46]. …”

[18F] AV-1451 uptake in corticobasal syndrome: the influence of beta-amyloid and clinical presentation

“…This may suggest that beta-amyloid deposition in these latter patients may instead reflect diffuse plaques consistent with pathological aging. Of four PiB(+) patients that have previously been reported in three previous studies [22, 33, 37], one patient similarly did not show any evidence for elevated ligand uptake [22], although this study used the [ 18 F]THK-5351 ligand.…”