Details

Autor(en) / Beteiligte

• Lannfelt, Lars
• Nilsberth, Camilla
• Westlind-Danielsson, Anita
• Eckman, Christopher B
• Condron, Margaret M
• Axelman, Karin
• Forsell, Charlotte
• Stenh, Charlotte
• Luthman, Johan
• Teplow, David B
• Younkin, Steven G
• Näslund, Jan

Titel

The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Aβ protofibril formation

Ist Teil von

• Nature neuroscience, 2001-09, Vol.4 (9), p.887-893

Ort / Verlag

Nature Publishing Group

Erscheinungsjahr

2001

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Several pathogenic Alzheimer's disease (AD) mutations have been described, all of which cause increased amyloid beta -protein (A beta ) levels. Here we present studies of a pathogenic amyloid precursor protein (APP) mutation, located within the A beta sequence at codon 693 (E693G), that causes AD in a Swedish family. Carriers of this 'Arctic' mutation showed decreased A beta 42 and A beta 40 levels in plasma. Additionally, low levels of A beta 42 were detected in conditioned media from cells transfected with APP sub(E693G). Fibrillization studies demonstrated no difference in fibrillization rate, but A beta with the Arctic mutation formed protofibrils at a much higher rate and in larger quantities than wild-type (wt) A beta . The finding of increased protofibril formation and decreased A beta plasma levels in the Arctic AD may reflect an alternative pathogenic mechanism for AD involving rapid A beta protofibril formation leading to accelerated buildup of insoluble A beta intra- and/or extracellularly.