p38 Kinase Is Activated in the Alzheimer's Disease Brain
Abstract
The p38 mitogen-activated protein kinase is a stress-activated enzyme responsible for transducing inflammatory signals and initiating apoptosis. In the Alzheimer's disease (AD) brain, increased levels of phosphorylated (active) p38 were detected relative to age-matched normal brain. Intense phospho-p38 immunoreactivity was associated with neuritic plaques, neuropil threads, and neurofibrillary tangle-bearing neurons. The antibody against phosphorylated p38 recognized many of the same structures as an antibody against aberrantly phosphorylated, paired helical filament (PHF) tau, although PHF-positive tau did not cross-react with the phospho-p38 antibody. These findings suggest a neuroinflammatory mechanism in the AD brain, in which aberrant protein phosphorylation affects signal transduction elements, including the p38 kinase cascade, as well as cytoskeletal components.
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Elevated p38 activity is found in brains from patients with tauopathies and in transgenic AD mice models expressing human tau or mutant APP, both of which correlate with tau aggregation.
“Elevated p38 activity is found in brains from patients with tauopathies (145–147) and in transgenic AD mice models expressing human tau (148–150) or mutant APP (151), both of which correlate with tau aggregation.”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [145]
Phospho-p38 is found exclusively in cells with NFT or tau aggregates in AD cases, co-localizes with tau aggregates in tauopathic brains, and co-precipitates with insoluble tau in both human cases and transgenic AD mouse models.
“Phospho-p38 is found exclusively in cells with NFT or tau aggregates in AD cases (152,153), co-localizes with tau aggregates in tauopathic brains (145,154) and co-precipitates with insoluble tau in both human cases and transgenic AD mouse models (145,148).”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [145]
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- Authors
- Hensley, K., Floyd, R. A., Zheng, N., Nael, R., Robinson, K. A., Nguyen, X., Pye, Q. N., Stewart, C. A., Geddes, J., Markesbery, W. R., Patel, E., Johnson, G. V. W., & Bing, G.
- Affiliations
- Oklahoma Medical Research Foundation (US)
- University of Kentucky (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Hensley, Kenneth
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1999-05
- Volume
- 72
- Issue
- 5
- Pages
- 2053-2058
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1974198922
- Cited by
- 373
- References
- 2
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 10 · 2023: 12 · 2022: 15 · 2021: 14 · 2020: 13 · 2019: 13 · 2018: 7 · 2017: 12 · 2016: 7 · 2015: 13 · 2014: 13 · 2013: 14 · 2012: 13
- FWCI
- 11.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P01 AG 05119, P01AG005119)
- National Institute of Neurological Disorders and Stroke (NS 35747, R01NS035747)
- 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
- p38 MAPK, Alzheimer's disease, neuroinflammation, neuritic plaques, neurofibrillary tangles, neuropil threads, signal transduction, apoptosis
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Antibodies, Monoclonal, Brain, Cross Reactions, Enzyme Activation, Female, Humans, Immunohistochemistry, Male, Phosphorylation, Reference Values, Tissue Distribution, Blotting, Western, tau Proteins, Calcium-Calmodulin-Dependent Protein Kinases, Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases
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