Subcortical 18 F-AV-1451 binding patterns in progressive supranuclear palsy.

BACKGROUND: Accumulation of cortical and subcortical tau pathology is the primary pathological substrate for progressive supranuclear palsy (PSP). 18 F-AV-1451, a radiotracer that binds to the pathological tau protein, may be helpful for in vivo visualization and quantitation of tau pathology in PSP. OBJECTIVES: The objectives of this study were to investigate cortical and subcortical 18 F-AV-1451 binding patterns in patients with PSP. METHODS: We recruited 14 PSP patients and compared their cortical and subcortical binding patterns in 18 F-AV-1451 positron emission tomography (PET) studies with those of 15 Parkinson's disease (PD) patients and 15 healthy controls. RESULTS: In both the PD and PSP groups, subcortical 18 F-AV-1451 binding did not correlate with the severity of motor dysfunctions, and cortical binding did not differ between the controls and each patient group. However, the PSP patients showed greater 18 F-AV-1451 binding in the putamen, globus pallidus, subthalamic nucleus, and dentate nucleus when compared with the controls, whereas the PD patients showed lower 18 F-AV-1451 binding in the substantia nigra than controls. CONCLUSIONS: The PSP and PD patients showed distinct subcortical 18 F-AV-1451 binding patterns reflecting subcortical tau pathology in PSP and reduced nigral neuromelanin in PD. However, there was no correlation with the severity of motor dysfunction, no cortical regions with increased binding in PSP patients, and variable degrees of subcortical binding even in the controls. Therefore, the 18 F-AV-1451 PET may be less than ideal for assessing tau pathology in PSP. Further studies will be required to validate the clinical correlation and to understand the clinical utility of 18 F-AV-1451 PET for PSP patients. © 2016 International Parkinson and Movement Disorder Society.

Tau PET in Alzheimer disease and mild cognitive impairment.

OBJECTIVE: To investigate the topographical distribution of tau pathology and its effect on functional and structural changes in patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) by using (18)F-AV-1451 PET. METHODS: We included 20 patients with AD, 15 patients with MCI, and 20 healthy controls, and performed neuropsychological function tests, MRI, as well as (18)F-florbetaben (for amyloid) and (18)F-AV-1451 (for tau) PET scans. By using the regional volume-of-interest masks extracted from MRIs, regional binding values of standardized uptake value ratios and volumes were measured. We compared regional binding values among 3 diagnostic groups and identified correlations among the regional binding values, performance in each cognitive function test, and regional atrophy. RESULTS: (18)F-AV-1451 binding was increased only in the entorhinal cortex in patients with MCI, while patients with AD exhibited greater binding in most cortical regions. In the 35 patients with MCI and AD, (18)F-AV-1451 binding in most of the neocortex increased with a worsening of global cognitive function. The visual and verbal memory functions were associated with the extent of (18)F-AV-1451 binding, especially in the medial temporal regions. The (18)F-AV-1451 binding also correlated with the severity of regional atrophy of the cerebral cortex. CONCLUSIONS: Tau PET imaging with (18)F-AV-1451 could serve as an in vivo biomarker for the evaluation of AD-related tau pathology and monitoring disease progression. The accumulation of pathologic tau is more closely related to functional and structural deterioration in the AD spectrum than ß-amyloid.

In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum.

OBJECTIVE: To determine the in vivo cortical spreading pattern of tau and amyloid and to establish positron emission tomography (PET) image-based tau staging in the Alzheimer disease (AD) spectrum. METHODS: We included 195 participants (53 AD, 52 amnestic mild cognitive impairment [MCI], 23 nonamnestic MCI, and 67 healthy controls) who underwent 2 PET scans ((18) F-florbetaben for amyloid-ß and (18) F-AV-1451 for tau). We assumed that regions with earlier appearances of pathology may show increased binding in a greater number of participants and acquired spreading order of tau accumulation by sorting the regional frequencies of involvement. We classified each participant into image-based tau stage based on the Z score of the composite region for each stage. RESULTS: Tau accumulation was most frequently observed in the medial temporal regions and spread stepwise to the basal and lateral temporal, inferior parietal, posterior cingulate, and other association cortices, and then ultimately to the primary cortical regions. In contrast, amyloid accumulation was found with similar frequency in the diffuse neocortical areas and then finally spread to the medial temporal regions. The image-based tau stage correlated with the general cognitive status, whereas cortical thinning was found only in the advanced tau stages: medial temporal region in stage V and widespread cortex in stage VI. INTERPRETATION: Our PET study replicated postmortem spreading patterns of tau and amyloid-ß pathologies. Unlike the diffuse accumulation of amyloid throughout the neocortex, tau spreading occurred in a stepwise fashion through the networks. Image-based tau staging may be useful for the objective assessment of AD progression. Ann Neurol 2016;80:247-258.

Tau Accumulation in Primary Motor Cortex of Variant Alzheimer's Disease with Spastic Paraparesis.

We studied topographic distribution of tau and amyloid-ß in a patient with variant Alzheimer's disease with spastic paraparesis (VarAD) by comparing AD patients. The proband developed progressive memory impairment, dysarthria, and spastic paraparesis at age 23. Heterozygous missense mutation (L166P) was found in exon 6 of presenilin-1 gene. The proband showed prominently increased amyloid binding in striatum and cerebellum and asymmetrical tau binding in the primary sensorimotor cortex contralateral to the side more affected by spasticity. We suspect that upper motor neuron dysfunctions may be attributed to excessive abnormal tau accumulation rather than amyloid-ß in the primary motor cortex.