AV-1451 tau and β-amyloid positron emission tomography imaging in dementia with Lewy bodies.

Patients with probable dementia with Lewy bodies (DLB) often have Alzheimer's disease (AD)-related pathology. Our objective was to determine the pattern of positron emission tomography (PET) tau tracer AV-1451 uptake in patients with probable DLB, compared to AD, and its relationship to β-amyloid deposition on PET. Consecutive patients with clinically probable DLB (n = 19) from the Mayo Clinic Alzheimer's Disease Research Center underwent magnetic resonance imaging, AV-1451, and Pittsburgh compound-B (PiB) PET examinations. Age- and sex-matched groups of AD dementia (n = 19) patients and clinically normal controls (n = 95) from an epidemiological cohort served as a comparison groups. Atlas- and voxel-based analyses were performed. The AD dementia group had significantly higher AV-1451 uptake than the probable DLB group, and medial temporal uptake completely distinguished AD dementia from probable DLB. Patients with probable DLB had greater AV-1451 uptake in the posterior temporoparietal and occipital cortex compared to clinically normal controls, and in probable DLB, the uptake in these regions correlated with global cortical PiB uptake (Spearman rho = 0.63; p = 0.006). Medial temporal lobe AV-1451 uptake distinguishes AD dementia from probable DLB, which may be useful for differential diagnosis. Elevated posterior temporoparietal and occipital AV-1451 uptake in probable DLB and its association with global cortical PiB uptake suggest an atypical pattern of tau deposition in DLB. ANN NEUROL 2017;81:58-67.

Kantarci K ，Lowe VJ ，Boeve BF ，Senjem ML ，Tosakulwong N ，Lesnick TG ，Spychalla AJ ，Gunter JL ，Fields JA ，Graff-Radford J ，Ferman TJ ，Jones DT ，Murray ME ，Knopman DS ，Jack CR Jr ，Petersen RC ... -  《-》

Tau Positron Emission Tomographic Imaging in the Lewy Body Diseases.

Gomperts SN ，Locascio JJ ，Makaretz SJ ，Schultz A ，Caso C ，Vasdev N ，Sperling R ，Growdon JH ，Dickerson BC ，Johnson K ... -  《-》

Dementia with Lewy bodies: association of Alzheimer pathology with functional connectivity networks.

Dementia with Lewy bodies (DLB) is neuropathologically defined by the presence of α-synuclein aggregates, but many DLB cases show concurrent Alzheimer's disease pathology in the form of amyloid-β plaques and tau neurofibrillary tangles. The first objective of this study was to investigate the effect of Alzheimer's disease co-pathology on functional network changes within the default mode network (DMN) in DLB. Second, we studied how the distribution of tau pathology measured with PET relates to functional connectivity in DLB. Twenty-seven DLB, 26 Alzheimer's disease and 99 cognitively unimpaired participants (balanced on age and sex to the DLB group) underwent tau-PET with AV-1451 (flortaucipir), amyloid-β-PET with Pittsburgh compound-B (PiB) and resting-state functional MRI scans. The resing-state functional MRI data were used to assess functional connectivity within the posterior DMN. This was then correlated with overall cortical flortaucipir PET and PiB PET standardized uptake value ratio (SUVr). The strength of interregional functional connectivity was assessed using the Schaefer atlas. Tau-PET covariance was measured as the correlation in flortaucipir SUVr between any two regions across participants. The association between region-to-region functional connectivity and tau-PET covariance was assessed using linear regression. Additionally, we identified the region with highest and the region with lowest tau SUVrs (tau hot- and cold spots) and tested whether tau SUVr in all other brain regions was associated with the strength of functional connectivity to these tau hot and cold spots. A reduction in posterior DMN connectivity correlated with overall higher cortical tau- (r = -0.39, P = 0.04) and amyloid-PET uptake (r = -0.41, P = 0.03) in the DLB group, i.e. patients with DLB who have more concurrent Alzheimer's disease pathology showed a more severe loss of DMN connectivity. Higher functional connectivity between regions was associated with higher tau covariance in cognitively unimpaired, Alzheimer's disease and DLB. Furthermore, higher functional connectivity of a target region to the tau hotspot (i.e. inferior/medial temporal cortex) was related to higher flortaucipir SUVrs in the target region, whereas higher functional connectivity to the tau cold spot (i.e. sensory-motor cortex) was related to lower flortaucipir SUVr in the target region. Our findings suggest that a higher burden of Alzheimer's disease co-pathology in patients with DLB is associated with more Alzheimer's disease-like changes in functional connectivity. Furthermore, we found an association between the brain's functional network architecture and the distribution of tau pathology that has recently been described in Alzheimer's disease. We show that this relationship also exists in patients with DLB, indicating that similar mechanisms of connectivity-dependent occurrence of tau pathology might be at work in both diseases.

Schumacher J ，Gunter JL ，Przybelski SA ，Jones DT ，Graff-Radford J ，Savica R ，Schwarz CG ，Senjem ML ，Jack CR ，Lowe VJ ，Knopman DS ，Fields JA ，Kremers WK ，Petersen RC ，Graff-Radford NR ，Ferman TJ ，Boeve BF ，Thomas AJ ，Taylor JP ，Kantarci K ... -  《-》

Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease.

SEE SARAZIN ET AL DOI101093/BRAIN/AWW041 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: The advent of the positron emission tomography tracer (18)F-AV1451 provides the unique opportunity to visualize the regional distribution of tau pathology in the living human brain. In this study, we tested the hypothesis that tau pathology is closely linked to symptomatology and patterns of glucose hypometabolism in Alzheimer's disease, in contrast to the more diffuse distribution of amyloid-β pathology. We included 20 patients meeting criteria for probable Alzheimer's disease dementia or mild cognitive impairment due to Alzheimer's disease, presenting with a variety of clinical phenotypes, and 15 amyloid-β-negative cognitively normal individuals, who underwent (18)F-AV1451 (tau), (11)C-PiB (amyloid-β) and (18)F-FDG (glucose metabolism) positron emission tomography, apolipoprotein E (APOE) genotyping and neuropsychological testing. Voxel-wise contrasts against controls (at P < 0.05 family-wise error corrected) showed that (18)F-AV1451 and (18)F-FDG patterns in patients with posterior cortical atrophy ('visual variant of Alzheimer's disease', n = 7) specifically targeted the clinically affected posterior brain regions, while (11)C-PiB bound diffusely throughout the neocortex. Patients with an amnestic-predominant presentation (n = 5) showed highest (18)F-AV1451 retention in medial temporal and lateral temporoparietal regions. Patients with logopenic variant primary progressive aphasia ('language variant of Alzheimer's disease', n = 5) demonstrated asymmetric left greater than right hemisphere (18)F-AV1451 uptake in three of five patients. Across 30 FreeSurfer-defined regions of interest in 16 Alzheimer's disease patients with all three positron emission tomography scans available, there was a strong negative association between (18)F-AV1451 and (18)F-FDG uptake (Pearson's r = -0.49 ± 0.07, P < 0.001) and less pronounced positive associations between (11)C-PiB and (18)F-FDG (Pearson's r = 0.16 ± 0.09, P < 0.001) and (18)F-AV1451 and (11)C-PiB (Pearson's r = 0.18 ± 0.09, P < 0.001). Voxel-wise linear regressions thresholded at P < 0.05 (uncorrected) showed that, across all patients, younger age was associated with greater (18)F-AV1451 uptake in wide regions of the neocortex, while older age was associated with increased (18)F-AV1451 in the medial temporal lobe. APOE ϵ4 carriers showed greater temporal and parietal (18)F-AV1451 uptake than non-carriers. Finally, worse performance on domain-specific neuropsychological tests was associated with greater (18)F-AV1451 uptake in key regions implicated in memory (medial temporal lobes), visuospatial function (occipital, right temporoparietal cortex) and language (left > right temporoparietal cortex). In conclusion, tau imaging-contrary to amyloid-β imaging-shows a strong regional association with clinical and anatomical heterogeneity in Alzheimer's disease. Although preliminary, these results are consistent with and expand upon findings from post-mortem, animal and cerebrospinal fluid studies, and suggest that the pathological aggregation of tau is closely linked to patterns of neurodegeneration and clinical manifestations of Alzheimer's disease.

Ossenkoppele R ，Schonhaut DR ，Schöll M ，Lockhart SN ，Ayakta N ，Baker SL ，O'Neil JP ，Janabi M ，Lazaris A ，Cantwell A ，Vogel J ，Santos M ，Miller ZA ，Bettcher BM ，Vossel KA ，Kramer JH ，Gorno-Tempini ML ，Miller BL ，Jagust WJ ，Rabinovici GD ... -  《-》

Regional cortical perfusion on arterial spin labeling MRI in dementia with Lewy bodies: Associations with clinical severity, glucose metabolism and tau PET.

Nedelska Z ，Senjem ML ，Przybelski SA ，Lesnick TG ，Lowe VJ ，Boeve BF ，Arani A ，Vemuri P ，Graff-Radford J ，Ferman TJ ，Jones DT ，Savica R ，Knopman DS ，Petersen RC ，Jack CR ，Kantarci K ... -  《NeuroImage-Clinical》