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Changes in BACE1 and BACE2 Expresssion in Alzheimer's Disease and Down Syndrome
Author(s) -
Laux Ashley,
Webb Robin,
Holler Chris,
Dowling Amy,
Beckett Tina,
Murphy M. Paul
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.484.2
Subject(s) - amyloid precursor protein , alzheimer's disease , disease , amyloid precursor protein secretase , glyceraldehyde 3 phosphate dehydrogenase , gene expression , biology , neuroscience , medicine , pathology , gene , genetics
Progressive cognitive decline is seen in Alzheimer's disease (AD) and Down syndrome (DS). In both, the amyloid precursor protein (APP) is believed to cause the development of amyloid pathology in the brain with the β‐site APP cleaving enzymes 1 and 2 (BACE1 and BACE2) as rate limiting enzymes. Individuals with DS have an extra copy of both APP and BACE2 on chromosome 21. Despite well studied mechanisms behind the common pathology, not much is known about regulatory processes. Evaluation of gene and protein expression levels in disease and control samples were studied to identify key regulation factors. Quantitative RT‐PCR and Western blot were used to measure the relative mRNA and protein expression levels of APP, BACE1 and BACE2 in DS, Mild Cognitive Impairment (MCI), presymptomatic AD (PCAD), frontotemporal dementia (FTD) and AD. In DS; APP, BACE1 and BACE2 mRNA increased while GAPDH decreased. APP expression increased, BACE1 expression decreased, and no change was found in BACE2 expression. In AD, MCI, PCAD and FTD, BACE1 and BACE2 increased. Regulation of APP and BACE2 are likely due to gene dosage effect while GAPDH and BACE1 are transcriptionally controlled in DS. Upregulation of BACE1, BACE2 and APP are likely early effects of MCI and AD and may be driven by general neurodegenerative processes. Thus the pathology seen in DS is regulated by different mechanisms than those seen in MCI and AD. Supported by NIH NS058382.