Molecular mechanisms linking amyloid β toxicity and Tau hyperphosphorylation in Alzheimer׳s disease
Abstract
Neurofibrillary tangles (aggregates of cytoskeletal Tau protein) and senile plaques (aggregates mainly formed by amyloid β peptide) are two landmark lesions in Alzheimer׳s disease. Some researchers have proposed tangles, whereas others have proposed plaques, as primary lesions. For a long time, these were thought of as independent mechanisms. However, experimental evidence suggests that both lesions are intimately related. We review here some molecular pathways linking amyloid β and Tau toxicities involving, among others, glycogen synthase kinase 3β, p38, Pin1, cyclin-dependent kinase 5, and regulator of calcineurin 1. Understanding amyloid β and Tau toxicities as part of a common pathophysiological mechanism may help to find molecular targets to prevent or even treat the disease.
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Both amyloid-beta and tau are believed to synergistically drive neurodegenerative processes involved in AD.
“Both amyloid-beta and tau are believed to synergistically drive neurodegenerative processes involved in AD (Bloom, 2014; Lloret et al., 2015; Stancu, Vasconcelos, Terwel, & Dewachter, 2014).”
From Functional and structural connectome properties in the 5XFAD transgenic mouse model of Alzheimer’s disease (2018) · cites this paper as Lloret et al., 2015
AD is associated with significant amyloid-beta peptide accumulation, which is produced from APP by PSEN1 and PSEN2, leading to the hypothesis that it is a primary mechanism of neurodegeneration.
“AD is associated with significant amyloid-beta peptide accumulation, which is produced from APP by PSEN1 and PSEN2, leading to the hypothesis that it is a primary mechanism of neurodegeneration (Hardy & Selkoe, 2002; Lloret, Fuchsberger, Giraldo, & Vina, 2015).”
From Functional and structural connectome properties in the 5XFAD transgenic mouse model of Alzheimer’s disease (2018) · cites this paper as Lloret et al., 2015
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Dyall, S. C. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00052 · Cited by 943 · see citing works
The Proteasome and Oxidative Stress in Alzheimer's Disease
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“Both amyloid-beta and tau are believed to synergistically drive neurodegenerative processes involved in AD (Bloom, 2014; Lloret et al., 2015; Stancu, Vasconcelos, Terwel, & Dewachter, 2014).”
Background
- Authors
- Lloret, A., Fuchsberger, T., Giraldo, E., & Viña, J.
- Affiliations
- Universitat de València (ES)
- Corresponding author
- Viña, J.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 83
- Pages
- 186-191
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2021811797
- Cited by
- 135
- References
- 23
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 9 · 2023: 8 · 2022: 7 · 2021: 7 · 2020: 17 · 2019: 16 · 2018: 14 · 2017: 14 · 2016: 15 · 2015: 5
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministerio de Educación, Cultura y Deporte (ISCIII2012-RED-43-029, PROMETEO2014/056)
- Generalitat Valenciana
- European Commission
- INCLIVA Instituto de Investigación Sanitaria (EU-funded CM1001)
- Federación Española de Enfermedades Raras
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid-beta toxicity, tau hyperphosphorylation, neurofibrillary tangles, amyloid plaques, glycogen synthase kinase-3β, p38 MAPK, Pin1, cyclin-dependent kinase 5, molecular pathogenesis, therapeutic target
- MeSH terms
- Alzheimer Disease, Humans, Phosphorylation, Amyloid beta-Peptides, tau Proteins, Protein Aggregation, Pathological
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