title: The Arctic amyloid-β precursor protein (AβPP) mutation results in distinct plaques and accumulation of N- and C-truncated Aβ.
abstract: The Arctic (p. E693G) mutation in the amyloid-β precursor protein (AβPP) facilitates amyloid-β (Aβ) protofibril formation and generates clinical symptoms of Alzheimer's disease (AD). Here, molecular details of Aβ in post mortem brain were investigated with biochemical and morphological techniques. The basic structure of Arctic plaques resembled cotton wool plaques. However, they appeared ring-formed with Aβ42-specific antibodies, but were actually targetoid, since the periphery and center of many parenchymal Aβ deposits stained differently with mid-domain, N- and C-terminal Aβ antibodies. Aβ fibrils were similar in shape, albeit shorter than in sporadic AD brain, when examined by electron microscopy. Aβwild-type and Aβarctic codeposited and parenchymal deposits were highly enriched in both N- and C-terminally truncated Aβ. In contrast, cerebral amyloid angiopathy (CAA) contained a substantial amount of Aβ1-40. The absence of plaques with cores of fibrillary Aβ might be due to the scarcity of full-length Aβ, although other mechanisms could be involved. Our findings are discussed in relation to mechanisms and relevance of amyloid formation and to the clinical features of AD.
authors: Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
authors: Ola
authors: O
authors: Philipson
authors: Anna
authors: A
authors: Lord
authors: Maciej
authors: M
authors: Lalowski
authors: Rabah
authors: R
authors: Soliymani
authors: Marc
authors: M
authors: Baumann
authors: Johan
authors: J
authors: Thyberg
authors: Nenad
authors: N
authors: Bogdanovic
authors: Tommie
authors: T
authors: Olofsson
authors: Lars O
authors: LO
authors: Tjernberg
authors: Martin
authors: M
authors: Ingelsson
authors: Lars
authors: L
authors: Lannfelt
authors: Hannu
authors: H
authors: Kalimo
authors: Lars N G
authors: LN
authors: Nilsson
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D019943:Amino Acid Substitution / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D010446:Peptide Fragments / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D058225:Plaque, Amyloid / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D020033:Protein Isoforms