Format

Send to

Choose Destination
Sci Rep. 2014 Nov 20;4:7130. doi: 10.1038/srep07130.

DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease.

Author information

1
1] Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan [2] Research and Development Headquarters, Lion Corporation, 7-2-1 Hirai, Edogawa-ku, Tokyo 132-0035, Japan.
2
1] Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan [2] JST Precursory Research for Embryonic Science Technology (PREST) Project, 160-8582 Tokyo, Japan.
3
1] Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan [2] Department of Applied Biological Chemistry, Kinki University, 3327-204 Naka-machi, Nara 631-8505, Japan.
4
1] Choju Medical Institute, Fukushimura Hospital, 19-14 Yamanaka, Noyori-cho, Toyohashi, Aichi 441-8124, Japan [2] Department of Medicine for Aging in Place and Community-Based Medical Education, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
5
1] Department of Optical Imaging, Medical Photonics Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan [2] JST, ERATO, Sato project, Tokyo 160-8582, Japan.
6
School of Human Health Sciences, Kyoto University Graduate School of Medicine, 53 Shogoin kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
7
Choju Medical Institute, Fukushimura Hospital, 19-14 Yamanaka, Noyori-cho, Toyohashi, Aichi 441-8124, Japan.
8
Research and Development Headquarters, Lion Corporation, 7-2-1 Hirai, Edogawa-ku, Tokyo 132-0035, Japan.
9
1] Research and Development Headquarters, Lion Corporation, 7-2-1 Hirai, Edogawa-ku, Tokyo 132-0035, Japan [2] Ritsumeikan Global Innovation Research Organization, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan.
10
1] Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan [2] JST, ERATO, Sato project, Tokyo 160-8582, Japan.

Abstract

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.

PMID:
25410733
PMCID:
PMC5382699
DOI:
10.1038/srep07130
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center