RGD Reference Report - Decreased concentration of human kallikrein 6 in brain extracts of Alzheimer's disease patients. - Rat Genome Database

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Decreased concentration of human kallikrein 6 in brain extracts of Alzheimer's disease patients.

Authors: Zarghooni, M  Soosaipillai, A  Grass, L  Scorilas, A  Mirazimi, N  Diamandis, EP 
Citation: Zarghooni M, etal., Clin Biochem 2002 May;35(3):225-31.
RGD ID: 1358599
Pubmed: PMID:12074831   (View Abstract at PubMed)

BACKGROUND: The human kallikrein 6 gene (KLK6) encodes for a secreted serine protease, hK6, which is highly expressed in brain. Previous reports have associated hK6 with the pathogenesis of Alzheimer's disease. Our objective was to develop a highly sensitive immunoassay for hK6 and use it to examine the levels of hK6 in brain tissue extracts from Alzheimer's disease patients and control subjects. METHODS: We developed antibodies against hK6 and constructed a 'sandwich' type immunoassay. We then assessed levels of hK6 in brain extracts from normal individuals and patients with Alzheimer's disease. RESULTS: The hK6 assay was developed using a combination of two antibodies (a mouse monoclonal and a rabbit polyclonal). Purified recombinant hK6 was used as a calibrator. The detection limit of the assay was 0.05 microg/L. The intra and inter-assay coefficient of variation was less than 6.5%. We found no detectable cross-reactivity by the homologous proteins hK2, hK3, hK8, hK10, hK11, hK13 and hK14. The hK6 concentration in human brain tissue extracts from healthy (n = 24) and Alzheimer's patients (n = 55) were 10.1 +/- 1.0 and 3.39 +/- 0.26 mcirog/g of total protein (mean +/- SE), respectively (p < 0.001). Similar differences were seen when the tissues were stratified by brain region (occipital, parietal, frontal and temporal cortex). CONCLUSIONS: We conclude that the newly developed hK6 immunoassay is suitable for quantification of hK6 protein in biologic fluids and tissue extracts. The brain of Alzheimer's disease patients contains significantly less hK6 than the brain of nonaffected individuals. The possible connection of hK6 with the pathogenesis of Alzheimer's disease merits further investigation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease  IAGP 1358599 RGD 
Alzheimer's disease  ISOKLK6 (Homo sapiens)1358599; 1358599 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Klk6  (kallikrein related-peptidase 6)

Genes (Mus musculus)
Klk6  (kallikrein related-peptidase 6)

Genes (Homo sapiens)
KLK6  (kallikrein related peptidase 6)


Additional Information