tailieunhanh - Báo cáo khoa học: Physiochemical characterization of the Alzheimer’s disease-related peptides Ab1–42Arctic and Ab1–42wt

The amyloidbpeptide (Ab) is crucial for the pathogenesis of Alzheimer’s disease. Aggregation of monomeric Ab into insoluble amyloid fibrils proceeds through several soluble Abintermediates, including protofibrils, which are believed to be central in the disease process. The main reason for this is their implication in familial Alzheimer’s disease with the Arctic amyloid precursor protein mutation (E693G). | iFEBS Journal Physiochemical characterization of the Alzheimer s disease-related peptides Ap1-42Arctic and Ap1-42wt Ann-Sofi Johansson1 Fredrik Berglind-Dehlin1 Goran Karlsson2 Katarina Edwards2 Par Gellerfors1 and Lars Lannfelt1 1 Department of Public Health and Caring Sciences Uppsala University Rudbeck Laboratory Sweden 2 Department of PhysicalChemistry Uppsala University Sweden Keywords amyloid-b Arctic fibrillization oligomerization protofibrils Correspondence . Johansson Department of Public Health and Caring Sciences Rudbeck Laboratory Dag Hammarskjolds vag 20 SE-75185 Uppsala Sweden Fax 46 18 4714808 Tel 46 18 4715030 E-mail Received 19 January 2006 revised 5 April 2006 accepted 10 April 2006 doi The amyloid b peptide Ab is crucial for the pathogenesis of Alzheimer s disease. Aggregation of monomeric Ab into insoluble amyloid fibrils proceeds through several soluble Ab intermediates including protofibrils which are believed to be central in the disease process. The main reason for this is their implication in familial Alzheimer s disease with the Arctic amyloid precursor protein mutation E693G . This mutation gives rise to early onset Alzheimer s disease and synthetic Ab1-40Arctic displays an enhanced rate of protofibril formation in vitro Nilsberth C Westlind-Dan-ielsson A Eckman CB Condron MM Axelman K Forsell C Stenh C Luthman J Teplow DB Younkin SG Naslund J Lannfelt L. 2001 Nat Neurosci 4 887-893 . To increase our understanding of the mechanisms involved in Ab aggregation especially Ab monomer oligomerization into protofibrils and protofibril fibrillization into fibrils the kinetics of Ab1-42wt and Ab1-42Arctic aggregation were examined under different physiochemical conditions such as concentration temperature ionic strength and pH. We used size exclusion chromatography for this purpose where monomers are separated from protofibrils and fibrils are separated from protofibrils in a .

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