title: DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease.
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.
authors.affiliation: 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.
authors.forename: Dai
authors.initials: D
authors.lastname: Yuki
authors.affiliation: 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.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sugiura
authors.affiliation: 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.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Zaima
authors.affiliation: 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.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Akatsu
authors.affiliation: 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.
authors.forename: Shiro
authors.initials: S
authors.lastname: Takei
authors.affiliation: 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.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yao
authors.affiliation: School of Human Health Sciences, Kyoto University Graduate School of Medicine, 53 Shogoin kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Maesako
authors.affiliation: School of Human Health Sciences, Kyoto University Graduate School of Medicine, 53 Shogoin kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Ayae
authors.initials: A
authors.lastname: Kinoshita
authors.affiliation: Choju Medical Institute, Fukushimura Hospital, 19-14 Yamanaka, Noyori-cho, Toyohashi, Aichi 441-8124, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Research and Development Headquarters, Lion Corporation, 7-2-1 Hirai, Edogawa-ku, Tokyo 132-0035, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kon
authors.affiliation: 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.
authors.forename: Keikichi
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: 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.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001344:Autopsy; D001923:Brain Chemistry; D016923:Cell Death; D018450:Disease Progression; D000076122:Disks Large Homolog 4 Protein; D004281:Docosahexaenoic Acids / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D066128:Gray Matter / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013569:Synapses / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010713:Phosphatidylcholines; C569014:SYP protein, human; D016708:Synaptophysin; D004281:Docosahexaenoic Acids