Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease
| Autor: | Suzanne L. Baker, Jacob W. Vogel, Andreas Lazaris, Michael Schöll, Averill Cantwell, Joel H. Kramer, Rik Ossenkoppele, William J. Jagust, Keith A. Vossel, Nagehan Ayakta, Bruce L. Miller, Maria Luisa Gorno-Tempini, Brianne M. Bettcher, Samuel N. Lockhart, Miguel Santos, Mustafa Janabi, Daniel R. Schonhaut, Gil D. Rabinovici, James P. O'Neil, Zachary A. Miller |
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| Přispěvatelé: | Neurology, Amsterdam Neuroscience - Neurodegeneration |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Male cognition Pathology Aging Disease Neuropsychological Tests Neurodegenerative Alzheimer's Disease Medical and Health Sciences 0302 clinical medicine 80 and over 2.1 Biological and endogenous factors tau Aetiology Aged 80 and over screening and diagnosis Aniline Compounds medicine.diagnostic_test Neurodegeneration Brain Human brain Middle Aged Detection medicine.anatomical_structure Positron emission tomography Neurological Biomedical Imaging Female Alzheimer's disease Psychology Alzheimer’s disease APOE 4.2 Evaluation of markers and technologies medicine.medical_specialty Amyloid tau Proteins Neuroimaging 03 medical and health sciences Apolipoproteins E Alzheimer Disease Fluorodeoxyglucose F18 Clinical Research mental disorders medicine Acquired Cognitive Impairment Dementia Humans Cognitive Dysfunction Benzothiazoles Aged Neurology & Neurosurgery Psychology and Cognitive Sciences Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) medicine.disease Brain Disorders Thiazoles 030104 developmental biology Glucose AV1451 PET Positron-Emission Tomography Case-Control Studies Neurology (clinical) Neuroscience 030217 neurology & neurosurgery Carbolines |
| Zdroj: | Brain : a journal of neurology, vol 139, iss Pt 5 Brain, 139, 1551-1567. Oxford University Press Ossenkoppele, R, Schonhaut, D R, Schoell, M, Lockhart, S N, Ayakta, N, Baker, S L, O'Neil, J P, Janabi, M, Lazaris, A, Cantwell, A, Vogel, J, Santos, M, Miller, Z A, Bettcher, B M, Vossel, K A, Kramer, J H, Gorno-Tempini, M L, Miller, B L, Jagust, W J & Rabinovici, G D 2016, ' Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease ', Brain, vol. 139, pp. 1551-1567 . https://doi.org/10.1093/brain/aww027 Ossenkoppele, R; Schonhaut, DR; Schöll, M; Lockhart, SN; Ayakta, N; Baker, SL; et al.(2016). Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease. Brain, 139(5), 1551-1567. doi: 10.1093/brain/aww027. UC Berkeley: Retrieved from: http://www.escholarship.org/uc/item/99g11755 |
| ISSN: | 0006-8950 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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