S100A7, a Novel Alzheimers Disease Biomarker with Non-Amyloidogenic α-Secretase Activity Acts via Selective Promotion of ADAM-10 英文参考文献.docVIP

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S100A7, a Novel Alzheimers Disease Biomarker with Non-Amyloidogenic α-Secretase Activity Acts via Selective Promotion of ADAM-10 英文参考文献.doc

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S100A7, a Novel Alzheimers Disease Biomarker with Non-Amyloidogenic α-Secretase Activity Acts via Selective Promotion of ADAM-10 英文参考文献

S100A7,aNovelAlzheimer’sDiseaseBiomarkerwith Non-Amyloidogenica-SecretaseActivityActsvia SelectivePromotionofADAM-10 WeipingQin1,LapHo1,3,JunWang1,3,ElainePeskind4,GiulioMariaPasinetti1,2,3* 1Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, United States of America, 2Department of Neuroscience, Mount Sinai School of Medicine,NewYork,NewYork,UnitedStatesofAmerica,3GeriatricResearchandClinicalCenter(GCRC),JamesJ.PetersVeteranAffairsMedicalCenter,Bronx,NewYork, UnitedStatesofAmerica,4UniversityofWashingtonSchoolofMedicine,Seattle,Washington,UnitedStatesofAmerica Abstract Alzheimer’sdisease(AD)isthemostcommoncauseofdementiaamongolderpeople.Atpresent,thereisnocureforthe disease and as of now there are no early diagnostic tests for AD. There is an urgency to develop a novel promising biomarker for early diagnosis of AD. Using surface-enhanced laser desorption ionization-mass spectrometry SELDI-(MS) proteomic technology, we identified and purified a novel 11.7-kDa metal- binding protein biomarker whose content is increased in the cerebrospinal fluid (CSF) and in the brain of AD dementia subjects as a function of clinical dementia. Following purification and protein-sequence analysis, we identified and classified this biomarker as S100A7, a protein knowntobeinvolvedinimmuneresponses.Usinganadenoviral-S100A7expressionsystem,wecontinuedtoexaminethe potentialroleofS100A7inADamyloidneuropathologyininvitromodelofAD.Wefoundthattheexpressionofexogenous S100A7inprimarycortico-hippocampalneuronculturesderivedfromTg2576transgenicembryosinhibitsthegenerationof b-amyloid (Ab)1–42 and Ab1–40 peptides, coincidental with a selective promotion of ‘‘non- amyloidogenic’’ a-secretase activityviapromotionofADAM(adisintegrinandmetalloproteinase)-10.Finally,aselectiveexpressionofhumanS100A7in thebrainoftransgenicmiceresultsinsignificantpromotionofa-secretaseactivity.Ourstudyforthefirsttimesuggeststhat S100A7maybeanovelbiomarkerofADdementiaandsupportsthehypothesisth