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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.


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The compositional ratio of PC(18:0/22:6) did not decrease in the brain of an Amyloid precursor protein-transgenic (APP-tg) mouse.(a) Shown are the KB-stained sections and mass spectrometry (MS) images of the PC species in serial coronal sections of APP-tg (J20) and wild-type (WT) mice. The MS images are shown with 50 μm spatial resolution. The scale bars show 1 mm. (b) The graphs show the % change in the PC composition ratio between the APP-tg and WT mice in the gray matter. The data are shown as mean (SE). n = 3.
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f6: The compositional ratio of PC(18:0/22:6) did not decrease in the brain of an Amyloid precursor protein-transgenic (APP-tg) mouse.(a) Shown are the KB-stained sections and mass spectrometry (MS) images of the PC species in serial coronal sections of APP-tg (J20) and wild-type (WT) mice. The MS images are shown with 50 μm spatial resolution. The scale bars show 1 mm. (b) The graphs show the % change in the PC composition ratio between the APP-tg and WT mice in the gray matter. The data are shown as mean (SE). n = 3.

Mentions: Finally, to see if PC(18:0/22:6) was reduced at the Aβ-accumulating stage before the postsynaptic disruptions, we performed a distributional analysis of PC in the brain of the human amyloid precursor protein (APP) transgenic (APP-tg) mouse (Fig. 6). Fig. 6a shows the distribution of the PC species in the coronal brain sections of 10-month-old APP-tg and wild-type (WT) mice. As was the case in the human brains, the distributions of the PCs in mice showed clearly different patterns between the gray and white matter, and PC(18:0/22:6) was distributed mainly in the gray matter. We did not find any significant differences in the contents of PC(18:0/22:6) in the gray matter of WT and APP-tg mice (Fig. 6b).


DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease
The compositional ratio of PC(18:0/22:6) did not decrease in the brain of an Amyloid precursor protein-transgenic (APP-tg) mouse.(a) Shown are the KB-stained sections and mass spectrometry (MS) images of the PC species in serial coronal sections of APP-tg (J20) and wild-type (WT) mice. The MS images are shown with 50 μm spatial resolution. The scale bars show 1 mm. (b) The graphs show the % change in the PC composition ratio between the APP-tg and WT mice in the gray matter. The data are shown as mean (SE). n = 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: The compositional ratio of PC(18:0/22:6) did not decrease in the brain of an Amyloid precursor protein-transgenic (APP-tg) mouse.(a) Shown are the KB-stained sections and mass spectrometry (MS) images of the PC species in serial coronal sections of APP-tg (J20) and wild-type (WT) mice. The MS images are shown with 50 μm spatial resolution. The scale bars show 1 mm. (b) The graphs show the % change in the PC composition ratio between the APP-tg and WT mice in the gray matter. The data are shown as mean (SE). n = 3.
Mentions: Finally, to see if PC(18:0/22:6) was reduced at the Aβ-accumulating stage before the postsynaptic disruptions, we performed a distributional analysis of PC in the brain of the human amyloid precursor protein (APP) transgenic (APP-tg) mouse (Fig. 6). Fig. 6a shows the distribution of the PC species in the coronal brain sections of 10-month-old APP-tg and wild-type (WT) mice. As was the case in the human brains, the distributions of the PCs in mice showed clearly different patterns between the gray and white matter, and PC(18:0/22:6) was distributed mainly in the gray matter. We did not find any significant differences in the contents of PC(18:0/22:6) in the gray matter of WT and APP-tg mice (Fig. 6b).

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.


Related in: MedlinePlus