Emerging roles of N- and C-terminally truncated Abeta species in Alzheimer's disease

摘要

ABSTRACT Introduction: Alzheimer's disease (AD) is characterized by a cerebral accumulation and aggregation of amyloid-beta (Abeta) peptides, which mainly accumulate in the form of extracellular deposits. In addition to the well-described full-length peptides Abeta_(1-40) and Abeta_(1-42), a variety of amino- and carboxy-terminally truncated Abeta variants have been identified in brain samples from sporadic and familial AD cases. Areas covered: This review gives an overview on the role of truncated Abeta species in human AD, as well as in transgenic AD mouse models. We outline the relevance of the most abundant N- and C-truncated Abeta species, highlight potential mechanisms with regard to their generation and discuss their suitability as targets for pharmacological interventions. Expert opinion: A variety of recent clinical trials aiming either at a reduced Abeta production by the use of secretase inhibitors or at increased Abeta clearance by the use of immunotherapy were terminated unsuccessfully. Truncated or post-translationally modified Abeta peptides are becoming increasingly recognized as important players in the etiology of AD and a more thorough comprehension of their cellular origin and biochemical peculiarities might break new ground for therapeutic strategies.