Synergistic interaction between amyloid and tau predicts the progression to dementia
Open accessAbstract
Introduction: Recent literature proposes that amyloid β (Aβ) and phosphorylated tau (p‐tau) synergism accelerates biomarker abnormalities in controls. Yet, it remains to be answered whether this synergism is the driving force behind Alzheimer disease (AD) dementia. Methods: We stratified 314 mild cognitive impairment individuals using [ 18 F]florbetapir positron emission tomography Aβ imaging and cerebrospinal fluid p‐tau. Regression and voxel‐based logistic regression models with interaction terms evaluated 2‐year changes in cognition and clinical status as a function of baseline biomarkers. Results: We found that the synergism between [ 18 F]florbetapir and p‐tau, rather than their additive effects, was associated with the cognitive decline and progression to AD. Furthermore, voxel‐based analysis revealed that temporal and inferior parietal were the regions where the synergism determined an increased likelihood of developing AD. Discussion: Together, the present results support that progression to AD dementia is driven by the synergistic rather than a mere additive effect between Aβ and p‐tau proteins.
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Human longitudinal studies show that a markedly increased risk of progression from mild cognitive impairment to AD is largely confined to individuals with concurrent Aβ and tau abnormalities, rather than those with only Aβ or only tau pathology.
“human longitudinal studies show that a markedly increased risk of progression from mild cognitive impairment to AD is largely confined to individuals with concurrent Aβ and tau abnormalities, rather than those with only Aβ or only tau pathology.”
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- Authors
- Pascoal, T. A., Mathotaarachchi, S., Shin, M., Benedet, A. L., Mohades, S., Wang, S., Beaudry, T., Kang, M. S., Soucy, J., Labbe, A., Gauthier, S., & Rosa‐Neto, P.
- Affiliations
- McGill University Research Centre for Studies in Aging (CA)
- Translational Neuroimaging Laboratory The McGill University Research Centre for Studies in Aging Montreal Canada
- Montreal Neurological Institute and Hospital (CA)
- Douglas Hospital Research Centre McGill University Montreal Canada
- Corresponding author
- Rosa‐Neto, Pedro
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2016-12-23
- Volume
- 13
- Issue
- 6
- Pages
- 644-653
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W2562384805
- Cited by
- 101
- References
- 40
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 7 · 2023: 14 · 2022: 12 · 2021: 15 · 2020: 15 · 2019: 11 · 2018: 11 · 2017: 6
- FWCI
- 8.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (MOP‐11‐51‐31)
- Alzheimer's Association (NIRG‐12‐92090, NIRP‐12‐259245)
- National Institutes of Health (U01 AG024904)
- U.S. Department of Defense (W81XWH‐12‐2‐0012)
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta, phosphorylated tau
- MeSH terms
- Aged, Alzheimer Disease, Aniline Compounds, Brain, Ethylene Glycols, Female, Follow-Up Studies, Humans, Male, Neuropsychological Tests, Biomarkers, Logistic Models, Amyloid beta-Peptides, tau Proteins, Disease Progression, Radiopharmaceuticals, Positron-Emission Tomography, Apolipoprotein E4, Cognitive Dysfunction
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