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

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

Research output: Contribution to journalArticle

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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 Ca(2+)-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 β-amyloid (Aβ) concentrations. Furthermore, RPH3A expression is selectively downregulated in cultured neurons treated with Aβ25-35 peptides. Our data suggest that presynaptic SNARE dysfunction forms part of the synaptopathology of AD.
Original languageEnglish
Pages (from-to)29-36
Number of pages8
JournalNeurochemistry International
Volume64
Early online date5 Nov 2013
DOIs
Publication statusPublished - Jan 2014

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Alzheimer Disease
SNARE Proteins
Neocortex
Neurofibrillary Tangles
Cholinergic Neurons
Synaptic Vesicles
Amyloid Plaques
Exocytosis
Amyloid
Cholinergic Agents
Neurotransmitter Agents
Dementia
Down-Regulation
rabphilin-3A
Ligands
Neurons
Peptides

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Decreased rabphilin 3A immunoreactivity in Alzheimer's disease is associated with Aβ burden. / Tan, Michelle G K; Lee, Chingli; Lee, Jasinda H; Francis, Paul T; Williams, Robert J; Ramírez, María J; Chen, Christopher P; Wong, Peter T-H; Lai, Mitchell K P.

In: Neurochemistry International, Vol. 64, 01.2014, p. 29-36.

Research output: Contribution to journalArticle

Tan, Michelle G K ; Lee, Chingli ; Lee, Jasinda H ; Francis, Paul T ; Williams, Robert J ; Ramírez, María J ; Chen, Christopher P ; Wong, Peter T-H ; Lai, Mitchell K P. / Decreased rabphilin 3A immunoreactivity in Alzheimer's disease is associated with Aβ burden. In: Neurochemistry International. 2014 ; Vol. 64. pp. 29-36.
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