The increased activity of BACE1 correlates with oxidative stress in Alzheimer's disease.
We evaluated expression, protein levels and activity of the Beta-site cleaving enzyme (BACE1) as well as the amount of products of lipid peroxidation in frontal cortex of three groups of cases: sporadic Alzheimer's disease (AD); control subjects (CTR); cognitively normal subjects with abundant amyloid plaques (NA). We found a significant increase of BACE1 activity and products of lipid peroxidation in brain tissue of AD cases, with normal gene expression, and non-significant elevation of protein levels. CTR and NA samples showed similar levels of BACE1 activity and oxidative products. BACE1 activity and the amount of oxidative products were significantly correlated in all cases.Moreover, both BACE1 activity and the level of 4-hydroxynonenal were correlated with the amount of Beta-amyloid pyroglutamated 3-42, the more toxic Beta-amyloid peptide that is characteristic of AD. These findings suggest that BACE1 activity reflects the type of ABeta species, rather than the Beta-amyloid plaques load. Hence, the increase of BACE1 activity occurring in sporadic AD is likely the effect, rather the cause, of ABeta accumulation and oxidative stress.
Borghi
Roberta
R
Department of Neuroscience, Ophthalmology and Genetics, University of Genova, Via De Toni 5, 16132 Genova, Italy. robertaborghi@yahoo.it
Patriarca
Stefania
S
Traverso
Nicola
N
Piccini
Alessandra
A
Storace
Daniela
D
Garuti
Anna
A
Gabriella Cirmena
Patrizio Odetti
Massimo Tabaton
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D015227:Lipid Peroxidation; D008875:Middle Aged; D018384:Oxidative Stress
D016229:Amyloid beta-Peptides; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human