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Distribution and Expression of Picalm in Alzheimer Disease
Open accessAbstract
PICALM, the gene encoding phosphatidylinositol-binding clathrin assembly (picalm) protein, was recently shown to be associated with risk of Alzheimer disease (AD). Picalm is a key component of clathrin-mediated endocytosis. It recruits clathrin and adaptor protein 2 (AP-2) to the plasma membrane and, along with, AP-2 recognizes target proteins. The attached clathrin triskelions cause membrane deformation around the target proteins enclosing them within clathrin-coated vesicles to be processed in lysosomes or endosomes. We examined the distribution of picalm in control and AD brain tissue and measured levels of picalm messenger RNA (mRNA) by real-time polymerase chain reaction. Immunolabeling of brain tissue showed that picalm is predominately present in endothelial cells. This was further supported by the demonstration of picalm in human cerebral microvascular cells grown in culture. Picalm mRNA was elevated in relation to glyceraldehyde-3-phosphate dehydrogenase but not factor VIII-related antigen or CD31 mRNA in the frontal cortex in AD. No change was seen in the temporal cortex or thalamus. The transport of Aβ across vessel walls and into the bloodstream is a major pathway of Aβ removal from the brain and picalm is ideally situated within endothelial cells to participate in this process. Further research is needed to determine whether PICALM expression is influenced by Aβ levels and whether it affects Aβ uptake and transport by endothelial cells.
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“Although our study indicates a reduced PICALM expression in LOAD-risk-allele iMGs, PICALM expression in patients with AD may also be influenced by cell type, MG state and disease stage31,56.”
From PICALM Alzheimer’s risk allele causes aberrant lipid droplets in microglia (2025) · cites this paper as [56]
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Endocytosis Is Required for Synaptic Activity-Dependent Release of Amyloid-β In Vivo
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Metadata
- Authors
- Baig, S., Joseph, S. A., Tayler, H., Abraham, R., Owen, M. J., Williams, J., Kehoe, P. G., & Love, S.
- Affiliations
- Frenchay Hospital (GB)
- Corresponding author
- Baig, Shabnam
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-10
- Volume
- 69
- Issue
- 10
- Pages
- 1071-1077
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC3017341
- OpenAlex
- W2010846728
- Cited by
- 115
- References
- 25
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 9 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 6 · 2018: 8 · 2017: 5 · 2016: 13 · 2015: 8 · 2014: 9 · 2013: 11 · 2012: 9
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Explore Bristol Research (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Funders
- Wellcome Trust
- Alzheimer's Society
- Alzheimer's Research Trust
- Medical Research Council (G0801418, G0300429)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- PICALM, Alzheimer's disease, clathrin-mediated endocytosis, endothelial cells, cerebral microvasculature, amyloid-beta transport, gene expression, mRNA distribution, brain tissue
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Factor VIII, Female, Gene Expression Regulation, Humans, Male, RNA, Messenger, Amyloid beta-Peptides, Statistics, Nonparametric, Platelet Endothelial Cell Adhesion Molecule-1, Monomeric Clathrin Assembly Proteins, Endothelial Cells
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