Mutations in the open reading frame of the β-site APP cleaving enzyme (BACE) locus are not a common cause of Alzheimer's disease

M. Nicolaou, Y. Q. Song, C. A. Sato, A. Orlacchio, T. Kawarai, H. Medeiros, Y. Liang, S. Sorbi, E. Richard, E. I. Rogaev, Y. Moliaka, A. C. Bruni, R. Jorge, M. Percy, R. Duara, L. A. Farrer, P. St George-Hyslop, E. A. Rogaeva

Research output: Contribution to journalArticle

Abstract

Amyloid β-peptide (Aβ) plays a central role in the pathogenesis of Alzheimer's disease (AD). The gene encoding the β-site APP cleaving enzyme (BACE), one of two enzymes that sequentially cleave the β-amyloid precursor protein to generate Aβ, has recently been cloned. We tested the hypothesis that BACE might be genetically associated with AD by linkage analysis (56 pedigrees), by direct nucleotide sequencing of the entire open reading frame (20 subjects with familial AD, and 10 subjects with sporadic AD) and by allelic association analysis (155 AD cases and 173 non-demented controls). Our results revealed no evidence for either genetic linkage or allelic association between BACE and AD, and no coding sequence mutations were detected in the open reading frame of the BACE gene. These data suggest that while BACE protein plays an important role in the pathogenesis of AD, and may be a robust therapeutic target, it is unlikely to be a major AD susceptibility locus.

Original languageEnglish
Pages (from-to)203-206
Number of pages4
JournalNeurogenetics
Volume3
Issue number4
DOIs
Publication statusPublished - 2001

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Keywords

  • β-site
  • Alzheimer's disease
  • APP cleaving enzyme
  • Linkage analysis

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)

Cite this

Nicolaou, M., Song, Y. Q., Sato, C. A., Orlacchio, A., Kawarai, T., Medeiros, H., Liang, Y., Sorbi, S., Richard, E., Rogaev, E. I., Moliaka, Y., Bruni, A. C., Jorge, R., Percy, M., Duara, R., Farrer, L. A., St George-Hyslop, P., & Rogaeva, E. A. (2001). Mutations in the open reading frame of the β-site APP cleaving enzyme (BACE) locus are not a common cause of Alzheimer's disease. Neurogenetics, 3(4), 203-206. https://doi.org/10.1007/s100480100123