title: Distribution and expression of picalm in Alzheimer disease.
abstract: 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.
authors.affiliation: Institute of Clinical Neurosciences, University of Bristol, Frenchay Hospital, Bristol, United Kingdom. shabnam.baig@bristol.ac.uk
authors.forename: Shabnam
authors.initials: S
authors.lastname: Baig
authors.forename: Sally A
authors.initials: SA
authors.lastname: Joseph
authors.forename: Hannah
authors.initials: H
authors.lastname: Tayler
authors.forename: Richard
authors.initials: R
authors.lastname: Abraham
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Julie
authors.initials: J
authors.lastname: Williams
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Kehoe
authors.forename: Seth
authors.initials: S
authors.lastname: Love
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D016229:Amyloid beta-Peptides; D034041:Monomeric Clathrin Assembly Proteins; C439003:PICALM protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; C078147:F8 protein, human; D005169:Factor VIII