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

Introduction: Alzheimer's disease (AD) is characterized by a cerebral accumulation and aggregation of amyloid-β (Aβ) peptides, which mainly accumulate in the form of extracellular deposits. In addition to the well-described full-length peptides Aβ1-40 and Aβ1-42, a variety of amino- and carboxy-terminally truncated Aβ 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 Aβ species in human AD, as well as in transgenic AD mouse models. We outline the relevance of the most abundant N- and C-truncated Aβ 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 Aβ production by the use of secretase inhibitors or at increased Aβ clearance by the use of immunotherapy were terminated unsuccessfully. Truncated or post-translationally modified Aβ 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.