The distribution and expression of picalm in Alzheimer's disease

SM Baig, SA Joseph, Hannah M Tayler, R Abraham, MJ Owen, J Williams, PG Kehoe, S Love

Research output: Contribution to journalArticle (Academic Journal)peer-review

76 Citations (Scopus)

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 (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 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.
Translated title of the contributionThe distribution and expression of picalm in Alzheimer's disease
Original languageEnglish
Pages (from-to)1071 - 1077
Number of pages7
JournalJournal of Neuropathology and Experimental Neurology
Volume69 (10)
DOIs
Publication statusPublished - Oct 2010

Bibliographical note

Publisher: Lippincott Williams and Wilkins

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