Local and distant relationships between amyloid, tau and neurodegeneration in Alzheimer's Disease
Open accessAbstract
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.
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The occurrence of NFTs correlates well with spatial patterns of neuronal loss and is related to the degree of cognitive deficits.
“The occurrence of NFTs correlates well with spatial patterns of neuronal loss and is related to the degree of cognitive deficits [3,4].”
From Diffusion tensor imaging reveals whole-brain microstructural changes in the P301L mouse model of tauopathy. (2020) · cites this paper as [3]
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Monoclonal Antibody Therapy in Alzheimer’s Disease
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Self-citationDefault mode network tau predicts future clinical decline in atypical early Alzheimer’s disease
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Self-citationHerpes simplex virus alters Alzheimer's disease biomarkers ‐ A hypothesis paper
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Deciphering the Interacting Mechanisms of Circadian Disruption and Alzheimer’s Disease
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Aβ and Tau Prions Causing Alzheimer’s Disease
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- Authors
- Iaccarino, L., Tammewar, G., Ayakta, N., Baker, S. L., Bejanin, A., Boxer, A. L., Gorno-Tempini, M. L., Janabi, M., Kramer, J. H., Lazaris, A., Lockhart, S. N., Miller, B. L., Miller, Z. A., O'Neil, J. P., Ossenkoppele, R., Rosen, H. J., Schonhaut, D. R., Jagust, W. J., & Rabinovici, G. D.
- Affiliations
- Vita-Salute San Raffaele University (IT)
- University of California, San Francisco (US)
- Lawrence Berkeley National Laboratory (US)
- University of California, Berkeley (US)
- Corresponding author
- Iaccarino, Leonardo
- ORCID
- Venue
- NeuroImage: Clinical
- Publisher
- Elsevier BV
- Published
- 2018
- Volume
- 17
- Pages
- 452-464
- ISSN
- 2213-1582 (ISSN-L)
- PMC
- PMC5684433
- OpenAlex
- W2756641284
- Cited by
- 165
- References
- 85
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 22 · 2023: 18 · 2022: 22 · 2021: 18 · 2020: 20 · 2019: 25 · 2018: 17
- FWCI
- 12.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage Clinical (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- University of California
- FP7 People: Marie-Curie Actions (628812)
- National Institutes of Health (K23-AG048291, R01-AG038791, U01-AG045390, U54-NS092089)
- Tau Consortium
- National Institute on Aging (F32-AG050389, P50-AG023501, R01-AG034570, R01-AG045611)
- John Douglas French Alzheimer's Foundation
- National Institute of Neurological Disorders and Stroke (R01-NS050915)
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Alzheimer's Association
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta, tau protein, neurodegeneration, 11C-PiB PET, gray matter volume reduction
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography
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