Altered enzymatic activity and allele frequency of OMI/HTRA2 in Alzheimer's disease.

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.

Behbahani, HomiraKarolinska Institutet (author)
Gellhaar, SandraKarolinska Institutet (author)
Forsell, CharlotteKarolinska Institutet (author)
Belin, Andrea CarmineKarolinska Institutet (author)
Anvret, Anna (author)
Zettergren, Anna,1978Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology(Swepub:gu)xhakan (author)
Nissbrandt, Hans,1952Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology(Swepub:gu)xnisha (author)
Lind, Charlotta (author)
Sydow, OlofKarolinska Institutet (author)
Graff, CarolineKarolinska Institutet (author)
Olson, LarsKarolinska Institutet (author)
Ankarcrona, MariaKarolinska Institutet (author)
Galter, DagmarKarolinska Institutet (author)
Karolinska InstitutetInstitutionen för neurovetenskap och fysiologi, sektionen för farmakologi (creator_code:org_t)

In:The FASEB journal : official publication of the Federation of American Societies for Experimental Biology: Wiley25:4, s. 1345-521530-6860
In:The FASEB Journal: Wiley25:4, s. 1345-520892-6638

By the author/editor: Westerlund, Mari ...; Behbahani, Homir ...; Gellhaar, Sandra; Forsell, Charlot ...; Belin, Andrea Ca ...; Anvret, Anna; show more...; Zettergren, Anna ...; Nissbrandt, Hans ...; Lind, Charlotta; Sydow, Olof; Graff, Caroline; Olson, Lars; Ankarcrona, Mari ...; Galter, Dagmar; show less...

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