title: Early intraneuronal accumulation and increased aggregation of phosphorylated Abeta in a mouse model of Alzheimer's disease.
abstract: The progressive accumulation of extracellular amyloid plaques in the brain is a common hallmark of Alzheimer's disease (AD). We recently identified a novel species of Aβ phosphorylated at serine residue 8 with increased propensity to form toxic aggregates as compared to non-phosphorylated species. The age-dependent analysis of Aβ depositions using novel monoclonal phosphorylation-state specific antibodies revealed that phosphorylated Aβ variants accumulate first inside of neurons in a mouse model of AD already at 2 month of age. At higher ages, phosphorylated Aβ is also abundantly detected in extracellular plaques. Besides a large overlap in the spatiotemporal deposition of phosphorylated and non-phosphorylated Aβ species, fractionized extraction of Aβ from brains revealed an increased accumulation of phosphorylated Aβ in oligomeric assemblies as compared to non-phosphorylated Aβ in vivo. Thus, phosphorylated Aβ could represent an important species in the formation and stabilization of neurotoxic aggregates, and might be targeted for AD therapy and diagnosis.
authors.affiliation: Department of Neurology, University of Bonn, 53127, Bonn, Germany.
authors.forename: Sathish
authors.initials: S
authors.lastname: Kumar
authors.forename: Oliver
authors.initials: O
authors.lastname: Wirths
authors.forename: Sandra
authors.initials: S
authors.lastname: Theil
authors.forename: Janina
authors.initials: J
authors.lastname: Gerth
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bayer
authors.forename: Jochen
authors.initials: J
authors.lastname: Walter
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides