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Decreased rabphilin 3A immunoreactivity in Alzheimer's disease is associated with Aβ burden

Research output: Contribution to journalArticle

Michelle G. K. Tan, Chingli Lee, Jasinda H. Lee, Paul T. Francis, Robert J. Williams, Maria J. Ramirez, Christopher P. Chen, Peter T. -H. Wong, Mitchell K. P. Lai

Original languageEnglish
Pages (from-to)29-36
Number of pages8
JournalNeurochemistry International
Volume64
DOIs
PublishedJan 2014

King's Authors

Abstract

Synaptic dysfunction, together with neuritic plaques, neurofibrillary tangles and cholinergic neuron loss is an established finding in the Alzheimer's disease (AD) neocortex. The synaptopathology of AD is known to involve both pre- and postsynaptic components. However, the status of rabphilin 3A (RPH3A), which interacts with the SNARE complex and regulates synaptic vesicle exocytosis and Ca2+-triggered neurotransmitter release, is at present unclear. In this study, we measured RPH3A and its ligand Rab3A as well as several SNARE proteins in postmortem neocortex of patients with AD, and found specific reductions of RPH3A immunoreactivity compared with aged controls. RPH3A loss correlated with dementia severity, cholinergic deafferentation, and increased beta-amyloid (A beta) concentrations. Furthermore, RPH3A expression is selectively downregulated in cultured neurons treated with A beta(25-35) peptides. Our data suggest that presynaptic SNARE dysfunction forms part of the synaptopathology of AD.

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