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Title | Amyloid precursor protein (APP) processing genes and cerebrospinal fluid APP cleavage product levels in Alzheimer's disease. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Bekris LM, Galloway NM, Millard S, Lockhart D, Li G, Galasko DR, Farlow MR, Clark CM, Quinn JF, Kaye JA, Schellenberg GD, Leverenz JB, Seubert P, Tsuang DW, Peskind ER, Yu CE |
Journal | Neurobiol Aging |
Volume | 32 |
Issue | 3 |
Pagination | 556.e13-23 |
Date Published | 2011 Mar |
ISSN | 1558-1497 |
Keywords | ADAM Proteins, ADAM10 Protein, Age of Onset, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Amyloid Precursor Protein Secretases, Apolipoprotein E4, Computational Biology, DNA Mutational Analysis, Female, Gene Frequency, Genotype, Humans, Male, Membrane Proteins, Middle Aged, Peptide Fragments, Polymorphism, Single Nucleotide |
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. |
DOI | 10.1016/j.neurobiolaging.2010.10.020 |
Alternate Journal | Neurobiol. Aging |
PubMed ID | 21196064 |
PubMed Central ID | PMC3065534 |
Grant List | R00 AG034214 / AG / NIA NIH HHS / United States P50 NS062684-02 / NS / NINDS NIH HHS / United States P50AGOO5131-27 / / PHS HHS / United States 1P50NS062684-01A1 / NS / NINDS NIH HHS / United States P50 AG005136 / AG / NIA NIH HHS / United States P50 AG005136-27 / AG / NIA NIH HHS / United States P50-AG005136 / AG / NIA NIH HHS / United States 2P50AG005136-27 / AG / NIA NIH HHS / United States K99 AG034214 / AG / NIA NIH HHS / United States P50 NS062684 / NS / NINDS NIH HHS / United States K99 AG034214-01A1 / AG / NIA NIH HHS / United States 1K99AGO34214-01A1 / / PHS HHS / United States |