Accumulation of cyclin-dependent kinase 5 (cdk5) in neurons with early stages of Alzheimer's disease neurofibrillary degeneration
Abstract
Cyclin-dependent kinase 5 (cdk5) is one of the candidate kinases involved in the abnormal hyperphosphorylation of tau. To have a direct effect on tau hyperphosphorylation, cdk5 protein levels and enzyme activity should be upregulated in especially those neurons that develop neurofibrillary tangles (NFTs). We studied the distribution of cdk5 immunoreactivity in neurons with or without early- and late-stage NFTs in hippocampal, entorhinal, transentorhinal, temporal and frontal cortices, and cerebellum of Alzheimer's disease (AD) and control brain. The immunocytochemical localisation of cdk5 was compared with that obtained using antibodies to PHF-tau (tau in paired helical filaments of NFTs, mAb AT8) and ubiquitin as markers of early and late stage NFTs, respectively. Immunoreactivities of cdk5 and PHF-tau were found in neuronal perikarya and processes of hippocampal, entorhinal, transentorhinal, temporal and frontal, and cerebellar cortices. An apparent increase of cdk5 immunoreactivity was seen in pretangle neurons and in neurons bearing early stage NFTs. These findings suggest that this kinase might be involved in the formation of NFTs at a relatively early stage in the neocortex.
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More than 20 serine/threonine kinases are reported to phosphorylate tau in vitro, including GSK-3β, Cdk5, MARK1-4, ERK, p38α MAPK, and JNK.
“In fact, there are currently more than 20 serine/threonine kinases reported to phosphorylate tau in vitro: glycogen synthase kinase 3 beta (GSK-3β), cyclin-dependent kinase 5 (Cdk5), microtubule affinity regulating kinase 1–4 (MARK1–MAPK4), extracellular signal-related kinase (ERK), p38 mitogen-associated protein kinase alpha (p38α MAPK), and c-Jun N-terminal kinase (JNK) are the best examples [19”
From Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology (2016) · cites this paper as [20]
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- Authors
- Pei, J.-J., Grundke-Iqbal, I., Iqbal, K., Bogdanovic, N., Winblad, B., & Cowburn, R. F.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Pei, Jin-Jing
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1998-06
- Volume
- 797
- Issue
- 2
- Pages
- 267-277
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W1979268652
- Cited by
- 226
- References
- 3
- Citations by year
- 2026: 2 · 2024: 8 · 2023: 5 · 2022: 3 · 2021: 2 · 2020: 7 · 2019: 5 · 2018: 8 · 2017: 3 · 2016: 2 · 2015: 7 · 2014: 9 · 2013: 11 · 2012: 11
- FWCI
- 6.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (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
- cyclin-dependent kinase 5, Alzheimer's disease, neurofibrillary tangles, tau hyperphosphorylation, PHF-tau, hippocampus, entorhinal cortex, neocortex, cerebellum
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Antibodies, Monoclonal, Antibody Specificity, Cerebral Cortex, Enzyme-Linked Immunosorbent Assay, Female, Hippocampus, Humans, Male, Middle Aged, Nerve Degeneration, Neurons, Phosphorylation, Temporal Lobe, Neurofibrillary Tangles, tau Proteins, Protein Serine-Threonine Kinases, Calcium-Calmodulin-Dependent Protein Kinases, Cyclin-Dependent Kinases, Glycogen Synthase Kinase 3, Cyclin-Dependent Kinase 5
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