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

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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.


Correlations between the compositional ratio of PC(18:0/22:6) in the gray matter versus Aβ deposition, disease duration of AD, and age at death.(a) The compositional ratio of PC(18:0/22:6) in the gray matter plotted against Aβ deposition in non-AD and AD patients. (b) The compositional ratio of PC(18:0/22:6) in the gray matter plotted against the disease duration of AD in non-AD and AD patients. (c) The compositional ratio of PC(18:0/22:6) in the gray matter plotted against age at death in non-AD and AD patients. The left panels show analyses of all of the patients (non-AD and AD). The right panels show analyses of the AD patients only. A Pearson's test was used to determine the correlations between parameters. = non-AD (n = 9);  = AD (n = 9). The colors of the markers indicate the Braak stages of each subject as shown in the top-right box.
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f4: Correlations between the compositional ratio of PC(18:0/22:6) in the gray matter versus Aβ deposition, disease duration of AD, and age at death.(a) The compositional ratio of PC(18:0/22:6) in the gray matter plotted against Aβ deposition in non-AD and AD patients. (b) The compositional ratio of PC(18:0/22:6) in the gray matter plotted against the disease duration of AD in non-AD and AD patients. (c) The compositional ratio of PC(18:0/22:6) in the gray matter plotted against age at death in non-AD and AD patients. The left panels show analyses of all of the patients (non-AD and AD). The right panels show analyses of the AD patients only. A Pearson's test was used to determine the correlations between parameters. = non-AD (n = 9); = AD (n = 9). The colors of the markers indicate the Braak stages of each subject as shown in the top-right box.

Mentions: To further investigate the relationship of PC(18:0/22:6) to AD, we performed correlative analyses between the compositional ratio of PC(18:0/22:6) and Aβ density in the gray matter. Both factors correlated negatively in the analysis of the all-subjects group (R = 0.545, P = 0.024) but not in the analysis of the AD patients group (R = 0.073, P = 0.781) (Fig. 4a). We then examined the correlation with disease duration and found it to be negatively correlated with the compositional ratio of PC(18:0/22:6), both in the analysis of the all-subjects group (R = 0.816, P = 0.001) and in the analysis of the AD patients group (R = 0.694, P = 0.002) (Fig. 4b). However, the compositional ratio of PC(18:0/22:6) was not significantly correlated with the age at death in the all-subjects group (R = 0.061, P = 0.817) but was positively correlated with the age at death in the AD patients group (R = 0.577, P = 0.015) (Fig. 4c). The compositional ratio of PC(18:0/22:6) in proportion to disease duration was independent of the age of the subjects. In addition, the decrease in PC(18:0/22:6) was remarkable in patients with Braak Stage VI.


DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease
Correlations between the compositional ratio of PC(18:0/22:6) in the gray matter versus Aβ deposition, disease duration of AD, and age at death.(a) The compositional ratio of PC(18:0/22:6) in the gray matter plotted against Aβ deposition in non-AD and AD patients. (b) The compositional ratio of PC(18:0/22:6) in the gray matter plotted against the disease duration of AD in non-AD and AD patients. (c) The compositional ratio of PC(18:0/22:6) in the gray matter plotted against age at death in non-AD and AD patients. The left panels show analyses of all of the patients (non-AD and AD). The right panels show analyses of the AD patients only. A Pearson's test was used to determine the correlations between parameters. = non-AD (n = 9);  = AD (n = 9). The colors of the markers indicate the Braak stages of each subject as shown in the top-right box.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Correlations between the compositional ratio of PC(18:0/22:6) in the gray matter versus Aβ deposition, disease duration of AD, and age at death.(a) The compositional ratio of PC(18:0/22:6) in the gray matter plotted against Aβ deposition in non-AD and AD patients. (b) The compositional ratio of PC(18:0/22:6) in the gray matter plotted against the disease duration of AD in non-AD and AD patients. (c) The compositional ratio of PC(18:0/22:6) in the gray matter plotted against age at death in non-AD and AD patients. The left panels show analyses of all of the patients (non-AD and AD). The right panels show analyses of the AD patients only. A Pearson's test was used to determine the correlations between parameters. = non-AD (n = 9); = AD (n = 9). The colors of the markers indicate the Braak stages of each subject as shown in the top-right box.
Mentions: To further investigate the relationship of PC(18:0/22:6) to AD, we performed correlative analyses between the compositional ratio of PC(18:0/22:6) and Aβ density in the gray matter. Both factors correlated negatively in the analysis of the all-subjects group (R = 0.545, P = 0.024) but not in the analysis of the AD patients group (R = 0.073, P = 0.781) (Fig. 4a). We then examined the correlation with disease duration and found it to be negatively correlated with the compositional ratio of PC(18:0/22:6), both in the analysis of the all-subjects group (R = 0.816, P = 0.001) and in the analysis of the AD patients group (R = 0.694, P = 0.002) (Fig. 4b). However, the compositional ratio of PC(18:0/22:6) was not significantly correlated with the age at death in the all-subjects group (R = 0.061, P = 0.817) but was positively correlated with the age at death in the AD patients group (R = 0.577, P = 0.015) (Fig. 4c). The compositional ratio of PC(18:0/22:6) in proportion to disease duration was independent of the age of the subjects. In addition, the decrease in PC(18:0/22:6) was remarkable in patients with Braak Stage VI.

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.