Axonal transport, tau protein, and neurodegeneration in Alzheimer's disease
Abstract
The molecular causes and the genetic and environmental modifying factors of the sporadic form of Alzheimer's disease (AD) remain elusive. Extrapolating from the known mutations that cause the rare familial forms and from the typical post-mortem pathological lesions in all AD patients--e.g., amyloid plaques and neurofibrillary tangles (NFTs)-the evident molecular candidates are amyloid precursor protein (APP), presenilin, and tau protein. To include ApoE4 as the only certain genetic modifier known leaves us to face the challenge of implementing these very different molecules into an evident pathological partnership. In more than one respect, the proposition of disturbed axonal transport appears attractive with more details becoming available on APP processing and microtubular transport and also of the pathology in the model systems--e.g., transgenic mice expressing APP or protein tau. Conversely, the resistance of APP-transgenic mice with full-blown amyloid pathology to also develop tau-related neurofibrillar pathology is a major challenge for this hypothesis. From the most relevant data discussed here, we conclude that the postulate of disturbed axonal transport as the primary event in AD is difficult to defend. On the other hand, failing axonal transport appears to be of major importance in the later stages in AD, by further compromising tau protein, APP metabolism, and synaptic functioning. Protein tau may thus be the central "executer" in the chain of events leading from a…
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Neurofibrillary tangles appear to be toxic since they are associated with impaired axonal transport, which provokes cell death.
“However, neurofibrillary tangles appear to be toxic since they are associated with impaired axonal transport, which provokes cell death (Stamer et al., 2002; Terwel et al., 2002; Cente et al., 2006; Smith et al., 2007).”
From The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer’s disease (2013) · cites this paper as Terwel et al., 2002
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- Authors
- Terwel, D., Dewachter, I., & Van Leuven, F.
- Affiliations
- KU Leuven (BE)
- Venue
- NeuroMolecular Medicine
- Published
- 2002
- Volume
- 2
- Issue
- 2
- Pages
- 151-166
- ISSN
- 1535-1084 (ISSN-L)
- OpenAlex
- W2094776926
- Cited by
- 146
- References
- 6
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 11 · 2023: 6 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 7 · 2018: 13 · 2017: 3 · 2016: 8 · 2015: 6 · 2014: 7 · 2013: 5 · 2012: 6
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroMolecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- Document Server@UHasselt (UHasselt) (submittedVersion)
- 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, axonal transport, tau protein, neurodegeneration, amyloid precursor protein, presenilin, APOE ε4, amyloid plaques, neurofibrillary tangles, tau hyperphosphorylation, microtubule destabilization, synaptic failure, APP transgenic mice, sporadic Alzheimer's disease
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Alzheimer Disease, Animals, Axons, Axonal Transport, Disease Models, Animal, Humans, Mice, Transgenic, Nerve Degeneration, Amyloid beta-Protein Precursor, Neurofibrillary Tangles, tau Proteins, Glycogen Synthase Kinase 3, Mice
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