Transcriptional and conformational changes of the tau molecule in Alzheimer's disease
Open accessAbstract
Mutations in the tau gene cause frontotemporal dementia with parkinsonism, presumably by affecting the balance between tau isoforms (with either three or four microtubule-binding repeats) or by impairing tau-tubulin binding. Although to date no mutations have been found for Alzheimer's disease, it is plausible that tangle pathology in this disorder is also driven by similar molecular modifications. Investigations of Alzheimer brain tissue with new technologies such as laser capture microscopy, quantitative PCR and fluorescence lifetime imaging will shed light on whether transcriptional or conformational alterations play a role in Alzheimer pathogenesis.
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4R tau expression is increased in vulnerable brain regions and NFT bearing neurons in AD brain.
“Expression of tau isoforms in AD brain is complicated; although it is still under debate that whether the overall 3R:4R tau ratio is altered, several studies support a notion that 4R tau expression is increased in vulnerable brain regions and NFT bearing neurons in AD brain [111, 113–118].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [116]
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“This strange conduct is because of conformational changes and misfolding in the primary structure of tau [20, 33–35] that prompts its abnormal aggregation to fibrillary assemblies inside the neurons of demented individuals [20, 36, 37].”
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“However, in AD, there is little evidence that increased tau precipitates tau pathology and neuronal loss [Hyman et al., 2005].”
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“16,17 In blood, AD patients with increasing clinical severity have concomitant increases in both P-tau and A-beta.”
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“…of β -amyloid protein (A β ) and aggregation of hyperphosphorylated Tau protein (microtubule-associated protein, MAP) represent the pathological hallmarks of plaque deposition and neurofibrillary tangles, respectively, and are key molecules for the diagnosis and classification of AD [ 160, 161 ].”
- Authors
- Hyman, B. T., Augustinack, J. C., & Ingelsson, M.
- Affiliations
- Massachusetts General Hospital (US)
- Corresponding author
- Hyman, Bradley T.
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 1739
- Issue
- 2-3
- Pages
- 150-157
- ISSN
- 0925-4439 (ISSN-L)
- OpenAlex
- W2037828638
- Cited by
- 79
- References
- 73
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 3 · 2014: 1 · 2013: 3 · 2012: 4
- FWCI
- 0.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- 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
- tau protein, Alzheimer's disease, tau gene mutations, frontotemporal dementia with parkinsonism, tau isoforms, microtubule-binding repeats, neurofibrillary tangles
- MeSH terms
- Alzheimer Disease, Humans, Microtubules, Mutation, Protein Conformation, Transcription, Genetic, Gene Expression, Neurofibrillary Tangles, tau Proteins, Alternative Splicing
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