Local and distant relationships between amyloid, tau and neurodegeneration in Alzheimer's Disease
Copyright policy )Local and distant relationships between amyloid, tau and neurodegeneration in Alzheimer's Disease
The relationships between β-amyloid (Aβ), tau and neurodegeneration within Alzheimer's Disease pathogenesis are not fully understood. To explore these associations in vivo, we evaluated 30 Aβ PET-positive patients (mean ± sd age 62.4 ± 8.3) with mild probable AD and 12 Aβ PET-negative healthy controls (HC) (mean ± sd age 77.3 ± 6.9) as comparison. All participants underwent 3 T MRI, 11C-PiB (Aβ) PET and 18F-AV1451 (tau) PET. Multimodal correlation analyses were run at both voxel- and region-of-interest levels. 11C-PiB retention in AD showed the most diffuse uptake pattern throughout association neocortex, whereas 18F-AV1451 and gray matter volume reduction (GMR) showed a progressive predilection for posterior cortices (p<0.05 Family-Wise Error-[FWE]-corrected). Voxel-level analysis identified negative correlations between 18F-AV1451 and gray matter peaking in medial and infero-occipital regions (p<0.01 False Discovery Rate-[FDR]-corrected). 18F-AV1451 and 11C-PiB were positively correlated in right parietal and medial/inferior occipital regions (p<0.001 uncorrected). 11C-PiB did not correlate with GMR at the voxel-level. Regionally, 18F-AV1451 was largely associated with local/adjacent GMR whereas frontal 11C-PiB correlated with GMR in posterior regions. These findings suggest that, in mild AD, tau aggregation drives local neurodegeneration, whereas the relationships between Aβ and neurodegeneration are not region specific and may be mediated by the interaction between Aβ and tau.
- Amsterdam UMC Netherlands
- Amsterdam University Medical Centers Netherlands
- Vita-Salute San Raffaele University Italy
- UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- University Medical Center United States
Magnetic Resonance Imaging (mesh), Male, Aging, Brain atrophy, Neurodegenerative, Acquired Cognitive Impairment (rcdc), Alzheimer's Disease, Clinical and health psychology, Aging (rcdc), Biomedical Imaging (rcdc), Brain Disorders (rcdc), Amyloid beta-Peptides (mesh), Neural Pathways, 80 and over, Dementia (rcdc), 80 and over (mesh), 2.1 Biological and endogenous factors, 32 Biomedical and Clinical Sciences (for-2020), Male (mesh), Neurosciences (rcdc), Neurodegenerative (rcdc), Alzheimer Disease (mesh), Aged, 80 and over, Humans (mesh), Tau imaging, Alzheimer's Disease (rcdc), Neural Pathways (mesh), Brain, Regular Article, Middle Aged, 3209 Neurosciences (for-2020), Magnetic Resonance Imaging, Neurological, 5203 Clinical and health psychology (for-2020), Biomedical Imaging, Female, Clinical Sciences, Computer applications to medicine. Medical informatics, Positron-Emission Tomography (mesh), R858-859.7, 610, tau Proteins, Amyloid imaging, Brain (mesh), Alzheimer Disease, 616, Middle Aged (mesh), Acquired Cognitive Impairment, Humans, RC346-429, 3202 Clinical Sciences (for-2020), Aged, Amyloid beta-Peptides, Biomedical and Clinical Sciences, Neurological (hrcs-hc), Aged (mesh), Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 2.1 Biological and endogenous factors (hrcs-rac), 1109 Neurosciences (for), Brain Disorders, 5202 Biological psychology (for-2020), Female (mesh), Positron-Emission Tomography, Biological psychology, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) (rcdc), Dementia, Neurology. Diseases of the nervous system, tau Proteins (mesh)
Magnetic Resonance Imaging (mesh), Male, Aging, Brain atrophy, Neurodegenerative, Acquired Cognitive Impairment (rcdc), Alzheimer's Disease, Clinical and health psychology, Aging (rcdc), Biomedical Imaging (rcdc), Brain Disorders (rcdc), Amyloid beta-Peptides (mesh), Neural Pathways, 80 and over, Dementia (rcdc), 80 and over (mesh), 2.1 Biological and endogenous factors, 32 Biomedical and Clinical Sciences (for-2020), Male (mesh), Neurosciences (rcdc), Neurodegenerative (rcdc), Alzheimer Disease (mesh), Aged, 80 and over, Humans (mesh), Tau imaging, Alzheimer's Disease (rcdc), Neural Pathways (mesh), Brain, Regular Article, Middle Aged, 3209 Neurosciences (for-2020), Magnetic Resonance Imaging, Neurological, 5203 Clinical and health psychology (for-2020), Biomedical Imaging, Female, Clinical Sciences, Computer applications to medicine. Medical informatics, Positron-Emission Tomography (mesh), R858-859.7, 610, tau Proteins, Amyloid imaging, Brain (mesh), Alzheimer Disease, 616, Middle Aged (mesh), Acquired Cognitive Impairment, Humans, RC346-429, 3202 Clinical Sciences (for-2020), Aged, Amyloid beta-Peptides, Biomedical and Clinical Sciences, Neurological (hrcs-hc), Aged (mesh), Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 2.1 Biological and endogenous factors (hrcs-rac), 1109 Neurosciences (for), Brain Disorders, 5202 Biological psychology (for-2020), Female (mesh), Positron-Emission Tomography, Biological psychology, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) (rcdc), Dementia, Neurology. Diseases of the nervous system, tau Proteins (mesh)
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