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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Characterization of PC molecular species in the human brain by Matrix-Assisted Laser Desorption/Ionization-Tandem Mass Spectrometry (MALDI-MS/MS).(a) The averaged mass spectra from m/z 750 to 900 in non-Alzheimer's Disease (AD; left panel) and AD brains (right panel). The annotations indicate peak assignments to the phosphatidylcholine (PC) molecular species with different fatty acid compositions. (b) The tandem mass spectrum of PC(16:0/18:1) at m/z 798 as an example of the molecular characterization by this technique. The product ions at m/z 739 and m/z 615 (from loss of trimethylamine [NL 59] and phosphocholine [NL 183] residues, respectively), were commonly observed ions formed from the PC species. The product ion at m/z 542 was assigned to a fragment that was formed by the neutral loss of palmitic acid (16:0). (c) The panel shows the structural formula for PC(16:0/18:1) and the assignment of the cleavage positions. NL, neutral loss.
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f1: Characterization of PC molecular species in the human brain by Matrix-Assisted Laser Desorption/Ionization-Tandem Mass Spectrometry (MALDI-MS/MS).(a) The averaged mass spectra from m/z 750 to 900 in non-Alzheimer's Disease (AD; left panel) and AD brains (right panel). The annotations indicate peak assignments to the phosphatidylcholine (PC) molecular species with different fatty acid compositions. (b) The tandem mass spectrum of PC(16:0/18:1) at m/z 798 as an example of the molecular characterization by this technique. The product ions at m/z 739 and m/z 615 (from loss of trimethylamine [NL 59] and phosphocholine [NL 183] residues, respectively), were commonly observed ions formed from the PC species. The product ion at m/z 542 was assigned to a fragment that was formed by the neutral loss of palmitic acid (16:0). (c) The panel shows the structural formula for PC(16:0/18:1) and the assignment of the cleavage positions. NL, neutral loss.

Mentions: First, we characterized the PC molecular species in the human brain with MALDI-IMS (Fig. 1). For this purpose, we performed a structural analysis with tandem mass spectrometry (MS/MS) directly on the coronal brain tissue sections of patients with and without AD. As a result, we identified six mass peaks for PCs with distinct fatty-acid compositions in both AD and non-AD specimens.


DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease
Characterization of PC molecular species in the human brain by Matrix-Assisted Laser Desorption/Ionization-Tandem Mass Spectrometry (MALDI-MS/MS).(a) The averaged mass spectra from m/z 750 to 900 in non-Alzheimer's Disease (AD; left panel) and AD brains (right panel). The annotations indicate peak assignments to the phosphatidylcholine (PC) molecular species with different fatty acid compositions. (b) The tandem mass spectrum of PC(16:0/18:1) at m/z 798 as an example of the molecular characterization by this technique. The product ions at m/z 739 and m/z 615 (from loss of trimethylamine [NL 59] and phosphocholine [NL 183] residues, respectively), were commonly observed ions formed from the PC species. The product ion at m/z 542 was assigned to a fragment that was formed by the neutral loss of palmitic acid (16:0). (c) The panel shows the structural formula for PC(16:0/18:1) and the assignment of the cleavage positions. NL, neutral loss.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382699&req=5

f1: Characterization of PC molecular species in the human brain by Matrix-Assisted Laser Desorption/Ionization-Tandem Mass Spectrometry (MALDI-MS/MS).(a) The averaged mass spectra from m/z 750 to 900 in non-Alzheimer's Disease (AD; left panel) and AD brains (right panel). The annotations indicate peak assignments to the phosphatidylcholine (PC) molecular species with different fatty acid compositions. (b) The tandem mass spectrum of PC(16:0/18:1) at m/z 798 as an example of the molecular characterization by this technique. The product ions at m/z 739 and m/z 615 (from loss of trimethylamine [NL 59] and phosphocholine [NL 183] residues, respectively), were commonly observed ions formed from the PC species. The product ion at m/z 542 was assigned to a fragment that was formed by the neutral loss of palmitic acid (16:0). (c) The panel shows the structural formula for PC(16:0/18:1) and the assignment of the cleavage positions. NL, neutral loss.
Mentions: First, we characterized the PC molecular species in the human brain with MALDI-IMS (Fig. 1). For this purpose, we performed a structural analysis with tandem mass spectrometry (MS/MS) directly on the coronal brain tissue sections of patients with and without AD. As a result, we identified six mass peaks for PCs with distinct fatty-acid compositions in both AD and non-AD specimens.

View Article: PubMed Central - PubMed

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.

No MeSH data available.