Novel abeta isoforms in Alzheimer's disease - their role in diagnosis and treatment.

摘要

The last decades have witnessed an explosion in studies of the role of amyloid-beta (Abeta) in the progress of the neurodegenerative disorder Alzheimer's disease (AD) and it is now widely accepted that Abeta is related to the pathogenesis of AD. For example, studies have shown that Abeta is neurotoxic and that the neurotoxicity of Abeta is related to its aggregation state. The concentration of the 42 amino acid form of Abeta (Abeta1-42) is reduced in the cerebrospinal fluid (CSF) from AD patients, which is believed to reflect the AD pathology with plaques in the brain acting as sinks. Less well investigated, however, is the ability of other Abeta isoforms to distinguish AD patients from controls and to identify treatment effects in clinical trials. Recently, novel C-truncated forms of Abeta (Abeta1-14, Abeta1-15, and Abeta1-16) were identified in human CSF. The presence of these small peptides is consistent with a catabolic amyloid precursor protein cleavage pathway by beta- followed by alpha-secretase. It has been shown that Abeta1-14, Abeta1-15, and Abeta1-16 increase dose-dependently in response to gamma-secretase inhibitor treatment while Abeta1-42 levels are unchanged. Here, we review the many aspects of Abeta and its isoforms with special focus on their potential role as diagnostic and theragnostic markers.