title: Occludin deficiency with BACE1 elevation in cerebral amyloid angiopathy.
abstract: OBJECTIVE
  A significant cause of spontaneous hemorrhages in the elderly is cerebral amyloid angiopathy (CAA), which causes degeneration of cerebral vessels, but the mechanisms are unclear.
  
  
  METHODS
  We isolated leptomeningeal vessels from rapidly autopsied brains (the average of postmortem intervals was 3.28 hours) from 9 patients with CAA and 10 age-matched controls, and used molecular, cell biology, and immunohistochemical approaches to examine β-site APP-cleaving enzyme 1 (BACE1) protein expression and enzymatic activities as well as tight junction molecular components in small- and medium-sized arteries of the cerebral cortex and leptomeninges.
  
  
  RESULTS
  We not only identified that the cerebral vessels, including leptomeningeal and cortical vessels, synthesize and express BACE1, but also found a significant elevation of both BACE1 protein levels and enzymatic activities in leptomeningeal vessels from patients with CAA. Moreover, overexpression of BACE1 in endothelial cells resulted in a significant reduction of occludin, a tight junction protein in blood vessels.
  
  
  CONCLUSIONS
  These findings suggest that in addition to neurons, cerebral vascular cells express functional BACE1. Moreover, elevated vascular BACE1 may contribute to deficiency of occludin in cerebral vessels, which ultimately has a critical role in pathogenesis of CAA and its related hemorrhage.
authors.affiliation: From the Department of Neurology (X.C., Q.D., Y.S.), Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China; Haldeman Laboratory of Molecular and Cellular Neurobiology (X.C., P.H., Y.S.), Sun Health Research Institute, Sun City, AZ; Center for Hormone Advanced Science and Education (P.H., R.L.) and Center for Advanced Therapeutic Strategies for Brain Disorders (P.H., Y.S.), Roskamp Institute, Sarasota, FL; and Department of Neurology (Y.S.), University of Florida College of Medicine, Gainesville.
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.forename: Hailan
authors.initials: H
authors.lastname: Yao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
authors.forename: Rena
authors.initials: R
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D016022:Case-Control Studies; D016657:Cerebral Amyloid Angiopathy / Q000201:enzymology* / Q000378:metabolism; D002536:Cerebral Arteries / Q000201:enzymology / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D008578:Meninges / Q000098:blood supply / Q000201:enzymology; D062793:Occludin / Q000172:deficiency*
chemical_list: D062793:Occludin; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
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