TY - JOUR
T1 - Decreased rabphilin 3A immunoreactivity in Alzheimer's disease is associated with Aβ burden
AU - Tan, Michelle G K
AU - Lee, Chingli
AU - Lee, Jasinda H
AU - Francis, Paul T
AU - Williams, Robert J
AU - Ramírez, María J
AU - Chen, Christopher P
AU - Wong, Peter T-H
AU - Lai, Mitchell K P
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84888248064&partnerID=8YFLogxK
UR - http://dx.doi.org/10.1016/j.neuint.2013.10.013
U2 - 10.1016/j.neuint.2013.10.013
DO - 10.1016/j.neuint.2013.10.013
M3 - Article
C2 - 24200817
SN - 0197-0186
VL - 64
SP - 29
EP - 36
JO - Neurochemistry International
JF - Neurochemistry International
ER -