期刊
ACTA NEUROPATHOLOGICA
卷 125, 期 5, 页码 699-709出版社
SPRINGER
DOI: 10.1007/s00401-013-1107-8
关键词
Post-translational modification; Phosphorylation; Alzheimer; Intraneuronal Abeta; Phospho amyloid; Transgenic mice
资金
- Deutsche Forschungsgemeinschaft (DFG) [WA1477/6, SFB645, KFo177]
- Alzheimer Forschung Initiative e.V. (AFI) [12854]
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 A beta phosphorylated at serine residue 8 with increased propensity to form toxic aggregates as compared to non-phosphorylated species. The age-dependent analysis of A beta depositions using novel monoclonal phosphorylation-state specific antibodies revealed that phosphorylated A beta variants accumulate first inside of neurons in a mouse model of AD already at 2 month of age. At higher ages, phosphorylated A beta is also abundantly detected in extracellular plaques. Besides a large overlap in the spatiotemporal deposition of phosphorylated and non-phosphorylated A beta species, fractionized extraction of A beta from brains revealed an increased accumulation of phosphorylated A beta in oligomeric assemblies as compared to non-phosphorylated A beta in vivo. Thus, phosphorylated A beta could represent an important species in the formation and stabilization of neurotoxic aggregates, and might be targeted for AD therapy and diagnosis.
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