Premium
Changes in β‐secretase activity in down syndrome and aging
Author(s) -
Webb Robin L.,
Holler Christopher J.,
Beckett Tina L.,
Head Elizabeth,
Murphy M. Paul
Publication year - 2009
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.23.1_supplement.671.9
Subject(s) - down syndrome , amyloid precursor protein , chromosome 21 , trisomy , disease , alzheimer's disease , gene isoform , molecular pathology , biology , gene , chromosome , medicine , genetics
Background Down Syndrome (DS) or trisomy 21, leads to Alzheimer's disease (AD) pathology by 40 years of age. Chromosome 21 harbors several genes implicated in AD, including the amyloid precursor protein (APP), and one isoform of the β‐site APP cleaving enzyme (BACE2). Objective Our laboratory is interested in β‐secretase and its regulation in different disease states. DS provides a unique model for evaluating changes in regulatory factors that influence the proportion of DS patients with AD. Methods We used a fluorometric assay developed in our lab to evaluate both BACE1 and BACE2 activity from a set of 24 DS (0.42‐62 years) and 16 control (0.45‐67 years) brains (Brodman area 9). Results and Conclusions BACE1 significantly decreased (p<0.04) with age, a finding differing from the situation seen in both AD and with normal aging in rodents and non‐human primates. Surprisingly, BACE2 was unchanged, even though the gene for BACE2 is located within the DS obligate region of chromosome 21. Finally, BACE1 and BACE2 activity levels were highly correlated in this series (r 2 = 0.95), indicating that there may be a higher degree of shared regulation than previously believed. Additional studies will examine the relationship between amyloid pathology and enzymatic activity. Insight gathered from these studies will help understand the nature of the shared pathology in both diseases. Supported by NIH NS058382.