Amyloid precursor protein (APP) processing genes and cerebrospinal fluid APP cleavage product levels in Alzheimer's disease

L. M. Bekris, N. M. Galloway, S. Millard, D. Lockhart, G. Li, D. R. Galasko, M. R. Farlow, C. M. Clark, J. F. Quinn, J. A. Kaye, G. D. Schellenberg, J. B. Leverenz, P. Seubert, D. W. Tsuang, E. R. Peskind, C. E. Yu

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The aim of this exploratory investigation was to determine if genetic variation within amyloid precursor protein (APP) or its processing enzymes correlates with APP cleavage product levels: APPα, APPβ or Aβ42, in cerebrospinal fluid (CSF) of cognitively normal subjects or Alzheimer's disease (AD) patients. Cognitively normal control subjects (n = 170) and AD patients (n = 92) were genotyped for 19 putative regulatory tagging SNPs within 9 genes (APP, ADAM10, BACE1, BACE2, PSEN1, PSEN2, PEN2, NCSTN and APH1B) involved in the APP processing pathway. SNP genotypes were tested for their association with CSF APPα, APPβ, and Aβ42, AD risk and age-at-onset while taking into account age, gender, race and APOE ε4. After adjusting for multiple comparisons, a significant association was found between ADAM10 SNP rs514049 and APPα levels. In controls, the rs514049 CC genotype had higher APPα levels than the CA, AA collapsed genotype, whereas the opposite effect was seen in AD patients. These results suggest that genetic variation within ADAM10, an APP processing gene, influences CSF APPα levels in an AD specific manner.

Original languageEnglish (US)
Pages (from-to)556.e13-556.e23
JournalNeurobiology of Aging
Volume32
Issue number3
DOIs
StatePublished - Mar 2011

Keywords

  • ADAM10
  • Alzheimer's
  • APH1B
  • APP
  • BACE1
  • BACE2
  • Cerebrospinal fluid
  • NCSTN
  • PEN2
  • PSEN1
  • PSEN2

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

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    Bekris, L. M., Galloway, N. M., Millard, S., Lockhart, D., Li, G., Galasko, D. R., Farlow, M. R., Clark, C. M., Quinn, J. F., Kaye, J. A., Schellenberg, G. D., Leverenz, J. B., Seubert, P., Tsuang, D. W., Peskind, E. R., & Yu, C. E. (2011). Amyloid precursor protein (APP) processing genes and cerebrospinal fluid APP cleavage product levels in Alzheimer's disease. Neurobiology of Aging, 32(3), 556.e13-556.e23. https://doi.org/10.1016/j.neurobiolaging.2010.10.020