title: Altered enzymatic activity and allele frequency of OMI/HTRA2 in Alzheimer's disease.
abstract: The serine-protease OMI/HTRA2, required for several cellular processes, including mitochondrial function, autophagy, chaperone activity, and apoptosis, has been implicated in the pathogenesis of both Alzheimer's disease (AD) and Parkinson's disease (PD). Western blot quantification of OMI/HTRA2 in frontal cortex of patients with AD (n=10) and control subjects (n=10) in two separate materials indicated reduced processed (active, 35 kDa) OMI/HTRA2 levels, whereas unprocessed (50 kDa) enzyme levels were not significantly different between the groups. Interestingly, the specific protease activity of OMI/HTRA2 was found to be significantly increased in patients with AD (n=10) compared to matched control subjects (n=10) in frontal cortex in two separate materials. Comparison of OMI/HTRA2 mRNA levels in frontal cortex and hippocampus, two brain areas particularly affected by AD, indicated similar levels in patients with AD (n=10) and matched control subjects (n=10). In addition, we analyzed the occurrence of the OMI/HTRA2 variants A141S and G399S in Swedish case-control materials for AD and PD and found a weak association of A141S with AD, but not with PD. In conclusion, our genetic, histological, and biochemical findings give further support to an involvement of OMI/HTRA2 in the pathology of AD; however, further studies are needed to clarify the role of this gene in neurodegeneration.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Westerlund
authors.forename: Homira
authors.initials: H
authors.lastname: Behbahani
authors.forename: Sandra
authors.initials: S
authors.lastname: Gellhaar
authors.forename: Charlotte
authors.initials: C
authors.lastname: Forsell
authors.forename: Andrea Carmine
authors.initials: AC
authors.lastname: Belin
authors.forename: Anna
authors.initials: A
authors.lastname: Anvret
authors.forename: Anna
authors.initials: A
authors.lastname: Zettergren
authors.forename: Hans
authors.initials: H
authors.lastname: Nissbrandt
authors.forename: Charlotta
authors.initials: C
authors.lastname: Lind
authors.forename: Olof
authors.initials: O
authors.lastname: Sydow
authors.forename: Caroline
authors.initials: C
authors.lastname: Graff
authors.forename: Lars
authors.initials: L
authors.lastname: Olson
authors.forename: Maria
authors.initials: M
authors.lastname: Ankarcrona
authors.forename: Dagmar
authors.initials: D
authors.lastname: Galter
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000201:enzymology; D005787:Gene Frequency; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006624:Hippocampus / Q000201:enzymology; D006801:Humans; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D010300:Parkinson Disease / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D012697:Serine Endopeptidases; C000615914:HTRA2 protein, human; D000074923:High-Temperature Requirement A Serine Peptidase 2