Spatial Relationships between Molecular Pathology and Neurodegeneration in the Alzheimer’s Disease Continuum
| Autor: | Julie Pham, Bruce L. Miller, Amelia Strom, Taylor J. Mellinger, William J. Jagust, Suzanne L. Baker, Renaud La Joie, David N Soleimani-Meigooni, Leonardo Iaccarino, Howard J. Rosen, Lauren Edwards, Gil D. Rabinovici, Mustafa Janabi, Daniel R. Schonhaut, Rik Ossenkoppele |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Aging Pathology Disease Neurodegenerative Neuropsychological Tests Alzheimer's Disease Pathogenesis Amyloid beta-Protein Precursor 80 and over 2.1 Biological and endogenous factors Psychology Medicine tau Aetiology Gray Matter Pathology Molecular Cognitive impairment Aged 80 and over Molecular pathology Neurodegeneration neurodegeneration amyloid Experimental Psychology Neurodegenerative Diseases Middle Aged Magnetic Resonance Imaging Neurological Biomedical Imaging Cognitive Sciences Original Article Female spatial extent medicine.medical_specialty Amyloid Cognitive Neuroscience tau Proteins Cellular and Molecular Neuroscience topography Clinical Research Alzheimer Disease mental disorders Acquired Cognitive Impairment Humans Dementia Cognitive Dysfunction Aged business.industry Neurosciences Molecular Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) medicine.disease Brain Disorders Positron-Emission Tomography business Spatial extent |
| Zdroj: | Cereb Cortex Cerebral cortex (New York, N.Y. : 1991), vol 31, iss 1 |
| ISSN: | 1460-2199 1047-3211 |
| DOI: | 10.1093/cercor/bhaa184 |
| Popis: | A deeper understanding of the spatial relationships of β-amyloid (Aβ), tau, and neurodegeneration in Alzheimer’s disease (AD) could provide insight into pathogenesis and clinical trial design. We included 81 amyloid-positive patients (age 64.4 ± 9.5) diagnosed with AD dementia or mild cognitive impairment due to AD and available 11C-PiB (PIB), 18F-Flortaucipir (FTP),18F-FDG-PET, and 3T-MRI, and 31 amyloid-positive, cognitively normal participants (age 77.3 ± 6.5, no FDG-PET). W-score voxel-wise deviation maps were created and binarized for each imaging-modality (W > 1.64, P tau > neurodegeneration was the most frequent hierarchy for both groups (79–77%, respectively), followed by tau > amyloid > neurodegeneration (13–10%) and amyloid > neurodegeneration > tau (6–13%). For symptomatic participants, most abnormal voxels were PIB+/FTP+/ND− (median 35%), and the great majority of ND+ voxels (91%) colocalized with molecular pathology. Amyloid spatially exceeded tau and neurodegeneration, with individual heterogeneities. Molecular pathology and neurodegeneration showed a progressive overlap along AD course, indicating shared vulnerabilities or synergistic toxic mechanisms. |
| Databáze: | OpenAIRE |
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