TY - JOUR
T1 - DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease
AU - Yuki, Dai
AU - Sugiura, Yuki
AU - Zaima, Nobuhiro
AU - Akatsu, Hiroyasu
AU - Takei, Shiro
AU - Yao, Ikuko
AU - Maesako, Masato
AU - Kinoshita, Ayae
AU - Yamamoto, Takayuki
AU - Kon, Ryo
AU - Sugiyama, Keikichi
AU - Setou, Mitsutoshi
N1 - Funding Information:
This research was supported by a WAKATE-S, KIBAN-B, Lipid machinery grant from the Japan Society for the Promotion of Science (to Mitsutoshi Setou) and Platform grant, Center of Innovation grant from Ministry of Education, Culture, Sports, Science and Technology in Japan. We thank Dr. Yoshio Hashizume for neuropathological support.
Publisher Copyright:
© 2014 Macmillan Publishers Limited. All rights reserved.
PY - 2014
Y1 - 2014
N2 - Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by senile plaques, neurofibrillary tangles, synaptic disruption, and neuronal loss. Several studies have demonstrated decreases of docosahexaenoic acid-containing phosphatidylcholines (DHA-PCs) in the AD brain. In this study, we used matrix-assisted laser desorption/ionization imaging mass spectrometry in postmortem AD brain to show that PC molecular species containing stearate and DHA, namely PC(18:0/22:6), was selectively depleted in the gray matter of patients with AD. Moreover, in the brain regions with marked amyloid β (Aβ) deposition, the magnitude of the PC(18:0/22:6) reduction significantly correlated with disease duration. Furthermore, at the molecular level, this depletion was associated with reduced levels of the postsynaptic protein PSD-95 but not the presynaptic protein synaptophysin. Interestingly, this reduction in PC(18:0/22:6) levels did not correlate with the degrees of Aβ deposition and neuronal loss in AD. The analysis of the correlations of key factors and disease duration showed that their effects on the disease time course were arranged in order as Aβ deposition, presynaptic disruption, postsynaptic disruption coupled with PC(18:0/22:6) reduction, and neuronal loss.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by senile plaques, neurofibrillary tangles, synaptic disruption, and neuronal loss. Several studies have demonstrated decreases of docosahexaenoic acid-containing phosphatidylcholines (DHA-PCs) in the AD brain. In this study, we used matrix-assisted laser desorption/ionization imaging mass spectrometry in postmortem AD brain to show that PC molecular species containing stearate and DHA, namely PC(18:0/22:6), was selectively depleted in the gray matter of patients with AD. Moreover, in the brain regions with marked amyloid β (Aβ) deposition, the magnitude of the PC(18:0/22:6) reduction significantly correlated with disease duration. Furthermore, at the molecular level, this depletion was associated with reduced levels of the postsynaptic protein PSD-95 but not the presynaptic protein synaptophysin. Interestingly, this reduction in PC(18:0/22:6) levels did not correlate with the degrees of Aβ deposition and neuronal loss in AD. The analysis of the correlations of key factors and disease duration showed that their effects on the disease time course were arranged in order as Aβ deposition, presynaptic disruption, postsynaptic disruption coupled with PC(18:0/22:6) reduction, and neuronal loss.
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U2 - 10.1038/srep07130
DO - 10.1038/srep07130
M3 - Article
C2 - 25410733
AN - SCOPUS:84923268372
SN - 2045-2322
VL - 4
JO - Scientific Reports
JF - Scientific Reports
M1 - 7130
ER -