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.
Highlights
Correspondence and requests for materials should be addressed to docosahexaenoic acid-containing phosphatidylcholines (DHA-PCs) and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer’s disease
With MatrixAssisted Laser Desorption/Ionization (MALDI)-Imaging Mass Spectrometry (IMS), we found that the ion intensities of DHA-PCs were decreased in the gray matter of the Alzheimer’s disease (AD) brains
In this study, we identified six PC species in the human brains that we examined with MALDI-IMS (Fig. 1)
Summary
Correspondence and requests for materials should be addressed to DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer’s disease. MatrixAssisted Laser Desorption/Ionization (MALDI)-IMS, in particular, is practical for analytical lipid studies, and this method has revealed the distribution of PC species in mouse and human brain tissues[27,28,29]. With this technique, we analyzed the distributional changes of DHAPCs in human brains with AD and in AD model mice and examined the association between DHA-PCs and aspects of neuronal loss and the decreases in synaptic proteins
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