Pyroglutamate-modified Aβ(3-42) affects aggregation kinetics of Aβ(1-42) by accelerating primary and secondary pathways

Pyroglutamate-modified Aβ(3-42) affects aggregation kinetics of Aβ(1-42) by accelerating primary and secondary pathways† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc04797a Click here for additional data file.

Synergistic Effect on Neurodegeneration by N-Truncated Aβ4−42 and Pyroglutamate Aβ3−42 in a Mouse Model of Alzheimer's Disease

The N-terminally truncated pyroglutamate Aβ3-42 (AβpE3-42) and Aβ4-42 peptides are known to be highly abundant in the brain of Alzheimer's disease (AD) patients. Both peptides show enhanced aggregation and neurotoxicity in comparison to full-length Aβ, suggesting that these amyloid peptides may play an important role in the pathogenesis of AD. The aim of the present work was to study the direct...

Activity and Architecture of Pyroglutamate-Modified Amyloid-β (AβpE3-42) Pores

Among the family of Aβ peptides, pyroglutamate-modified Aβ (AβpE) peptides are particularly associated with cytotoxicity in Alzheimer's disease (AD). They represent the dominant fraction of Aβ oligomers in the brains of AD patients, but their accumulation in the brains of elderly individuals with normal cognition is significantly lower. Accumulation of AβpE plaques precedes the formation of pla...

Alzheimer therapy with an antibody against N-terminal Abeta 4-X and pyroglutamate Abeta 3-X

Full-length Aβ1-42 and Aβ1-40, N-truncated pyroglutamate Aβ3-42 and Aβ4-42 are major variants in the Alzheimer brain. Aβ4-42 has not been considered as a therapeutic target yet. We demonstrate that the antibody NT4X and its Fab fragment reacting with both the free N-terminus of Aβ4-x and pyroglutamate Aβ3-X mitigated neuron loss in Tg4-42 mice expressing Aβ4-42 and completely rescued spatial re...

Lysosomal Enzyme Glucocerebrosidase Protects against Aβ1-42 Oligomer-Induced Neurotoxicity.

Glucocerebrosidase (GCase) functions as a lysosomal enzyme and its mutations are known to be related to many neurodegenerative diseases, including Gaucher's disease (GD), Parkinson's disease (PD), and Dementia with Lewy Bodies (DLB). However, there is little information about the role of GCase in the pathogenesis of Alzheimer's disease (AD). Here we demonstrate that GCase protein levels and enz...