Affiliations: [a] Department of Microbiology & Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark, NJ, USA | [b] Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
Correspondence:
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Correspondence to: Hieronim Jakubowski, Department of Microbiology & Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, 225 Warren Street Newark, NJ 07101-1709, USA. Tel.: +1 973 972 4483 ext. 28733; Fax: +1 973 972 8981; E-mail: jakubows@umdnj.edu.
Note: [1] Permanent affiliation: Institute of Bioorganic Chemistry, Poznan, Poland.
Note: [2] Permanent affiliation: Department of Medical Diagnostics, Faculty of Pharmacy, Jagiellonian University, Kraków, Poland.
Note: [] Handling Associate Editors: Jesus Avila, Sudha Seshadri
Abstract: Elevated plasma homocysteine (Hcy) is a risk factor for Alzheimer's disease (AD). Bleomycin hydrolase (BLH), a thiol-dependent enzyme that has Hcy-thiolactonase (HTase) and aminopeptidease (APase) activities, has also been implicated in Alzheimer's disease (AD). In order to examine its role in AD, BLH activities were measured in postmortem brain tissue from twelve AD patients and twelve control patients who died from non-neurological causes. We found that HTase and APase activities in human brain extracts were strongly correlated and sensitive to the thiol reagent iodoacetamide, indicating that they are associated with BLH. Both activities were significantly decreased in brain tissue extracts from AD patients relative to controls (7.6 ± 4.2 vs. 13.5 ± 5.5 units, p = 0.003 for HTase, and 3.82 ± 1.27 vs. 5.33 ± 1.68 units, p = 0.010 for APase). HTase and APase activities were positively correlated with N-linked protein Hcy, but not with tHcy, in AD and control brains. Levels of brain total Hcy and N-linked protein Hcy did not differ between AD cases and controls. These results suggest that diminished functional BLH activity could contribute to the pathology of AD.
