Involvement of WAVE Accumulation in Aβ/APP Pathology-Dependent Tangle Modification in Alzheimer’s Disease
Open accessAbstract
Synaptic deficits are closely correlated with cognitive dysfunction in Alzheimer's disease (AD), and synaptic integrity is regulated by the actin cytoskeleton. We demonstrated here that the Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE), a key molecule for actin assembly, co-aggregated with both hyperphosphorylated tau and phosphorylated collapsin response mediator protein 2 (CRMP2) in neurofibrillary tangles and abnormal neurites of the AD brain. Although phosphorylated CRMP2 accumulation was induced in the brains of JNPL3 mice, WAVE accumulation was not detected in the brains of either JNPL3 or Tg2576 mice that developed neurofibrillary tangles and amyloid-beta (Abeta) plaques, respectively. Interestingly, both phosphorylated CRMP2 accumulation and WAVE accumulation were recapitulated in the brains of 3xTg-AD mice that developed neurofibrillary tangles and Abeta plaques. In addition, we found an interaction between WAVE, CRMP2, and hyperphosphorylated tau in the cytosolic fraction of the AD brain. Taken together, WAVE accumulation may require both Abeta/amyloid precursor protein and tau pathologies, and an interaction between WAVE, CRMP2, and hyperphosphorylated tau may be involved in this process. Thus, WAVE accumulation may be involved in Abeta/amyloid precursor protein mediated-tangle modification, suggesting a possible correlation between WAVE accumulation and synaptic deficits induced by disturbances in actin assembly in AD brains.
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The colocalization of WAVE1 protein or phosphorylated WAVE1 with aggregated hyperphosphorylated tau was observed in the brains of triple transgenic mice and human AD patients.
“The colocalization of the WAVE1 protein or phosphorylated WAVE1 with aggregated hyperphosphorylated tau was observed in the brains of triple transgenic mice (APPswe/PS1M146V/tauP301L)47 and human AD patients147.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [147]
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Self-citationThe WAVE complex in developmental and adulthood brain disorders
Kim, H.-G., Berdasco, C., Nairn, A. C., & Kim, Y. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01386-w · Cited by 8 · see citing works
- Authors
- Takata, K., Kitamura, Y., Nakata, Y., Matsuoka, Y., Tomimoto, H., Taniguchi, T., & Shimohama, S.
- Affiliations
- Kyoto Pharmaceutical University (JP)
- Georgetown University Medical Center (US)
- Mie University (JP)
- Sapporo Medical University (JP)
- Corresponding author
- Kitamura, Yoshihisa
- Shimohama, Shun
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 175
- Issue
- 1
- Pages
- 17-24
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC2708790
- OpenAlex
- W2050106520
- Cited by
- 36
- References
- 2
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 5 · 2014: 1 · 2013: 6 · 2012: 7
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- University of Tokyo
- Japan Society for the Promotion of Science
- National Institute on Aging (R01AG026478, AG022455, K01AG022455, AG026478)
- 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
- waves, Alzheimer's disease, neurofibrillary tangles, amyloid plaques, tau hyperphosphorylation, CRMP2, actin cytoskeleton, synaptic dysfunction, Tg2576 mice, 3xTg-AD mice
- MeSH terms
- Aged, Alzheimer Disease, Animals, Brain, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Mice, Transgenic, Nerve Tissue Proteins, Phosphorylation, Blotting, Western, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Neurofibrillary Tangles, tau Proteins, Microscopy, Confocal, Intercellular Signaling Peptides and Proteins, Immunoprecipitation, Wiskott-Aldrich Syndrome Protein Family, Mice
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