title: Aβ38 in the brains of patients with sporadic and familial Alzheimer's disease and transgenic mouse models.
abstract: The pathogenesis of Alzheimer's disease (AD) is believed to be closely dependent on deposits of neurotoxic amyloid-β peptides (Aβ), which become abundantly present throughout the central nervous system in advanced stages of the disease. The different Aβ peptides existing are generated by subsequent cleavage of the amyloid-β protein precursor (AβPP) and may vary in length and differ at their C-terminus. Despite extensive studies on the most prevalent species Aβ40 and Aβ42, Aβ peptides with other C-termini such as Aβ38 have not received much attention. In the present study, we used a highly specific and sensitive antibody against Aβ38 to analyze the distribution of this Aβ species in cases of sporadic and familial AD, as well as in the brains of a series of established transgenic AD mouse models. We found Aβ38 to be present as vascular deposits in the brains of the majority of sporadic AD cases, whereas it is largely absent in non-demented control cases. Aβ38-positive extracellular plaques were virtually limited to familial cases. Interestingly we observed Aβ38-positive plaques not only among familial cases due to AβPP mutations, but also in cases of familial AD caused by presenilin (PSEN) mutations. Furthermore we demonstrate that Aβ38 deposits in the form of extracellular plaques are common in several AD transgenic mouse models carrying either only AβPP, or combinations of AβPP, PSEN1, and tau transgenes.
authors.affiliation: Division of Molecular Psychiatry, Department of Psychiatry, University Medicine Goettingen, Goettingen, Germany.
authors.forename: Jochim
authors.initials: J
authors.lastname: Reinert
authors.affiliation: Synaptic Systems GmbH, Goettingen, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Martens
authors.affiliation: Division of Molecular Psychiatry, Department of Psychiatry, University Medicine Goettingen, Goettingen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Huettenrauch
authors.affiliation: Synaptic Systems GmbH, Goettingen, Germany.
authors.forename: Tekla
authors.initials: T
authors.lastname: Kolbow
authors.affiliation: Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lannfelt
authors.affiliation: Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Ingelsson
authors.affiliation: Department of Pathology, University and University Hospital of Helsinki, Helsinki, Finland.
authors.forename: Anders
authors.initials: A
authors.lastname: Paetau
authors.affiliation: Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Auli
authors.initials: A
authors.lastname: Verkkoniemi-Ahola
authors.affiliation: Division of Molecular Psychiatry, Department of Psychiatry, University Medicine Goettingen, Goettingen, Germany.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bayer
authors.affiliation: Division of Molecular Psychiatry, Department of Psychiatry, University Medicine Goettingen, Goettingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Wirths
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078639:amyloid beta-protein (1-38)
keywords: Aβ$_{38}$; AβPP; amyloid; mutations; presenilin; transgenic mice; vasculature; vessels