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Background Studies have demonstrated that the levels of phospholipids, including phosphatidylinositols (PIs), were decreased in Alzheimer's disease (AD) brain, presenting as a potential biomarker for AD. The plasma phospholipids levels have also been discovered to predict the conversion of cognitively normal elderly adults to amnestic mild cognitive impairment (aMCI) or demented patients. Objective To investigate the expression profile of PIs in erythrocytes of AD and aMCI patients, which would serve as a blood-based method to distinguish AD and aMCI patients from normal controls (NC). Methods In this study, we used anion-exchange high-performance liquid chromatography to analyze PIs alterations in erythrocytes from a total of 86 prospectively recruited subjects (including 24 NC, 21 aMCI patients, and 41 AD patients). Results We found that the levels of PI40 : 4, PI3/5P, and PI(3,4)P2 in aMCI patients, and the levels of PI4P, PI(3,4)P2, and PI3/5P in AD patients were significantly decreased compared to NC. The changed expression profile of PIs could effectively discriminate AD and aMCI patients from NC (AUC = 0.964, 0.938, respectively). Conclusion The altered expression profile of erythrocytes PIs might be a potential blood-based biomarker for AD and aMCI. This alteration of PIs probably reflected the impaired deformability and oxygen-carrying capacity of erythrocytes in AD and aMCI patients.

Hyccin/FAM126A mutations are linked to hypomyelination and congenital cataract disease (HCC), but whether and how Hyccin/FAM126A deficiency causes hypomyelination remains undetermined. This study shows Hyccin/FAM126A expression was necessary for the expression of other components of the PI4KIIIα complex in Drosophila. Knockdown of Hyccin/FAM126A in glia reduced the enrichment of glial cells, disrupted axonal sheaths and visual ability in the visual system, and these defects could be fully rescued by overexpressing either human FAM126A or FAM126B, and partially rescued by overexpressing a plasma membrane-targeting recombinant mouse PI4KIIIα. Additionally, PI4KIIIα knockdown in glia phenocopied Hyccin/FAM126A knockdown, and this was partially rescued by overexpressing the recombinant PI4KIIIα, but not human FAM126A or FAM126B. This study establishes an animal model of HCC and indicates that Hyccin/FAM126A plays an essential role in glial enrichment and axonal sheath in a cell-autonomous manner in the visual system via controlling the expression and stabilization of the PI4KIIIα complex at the plasma membrane.

The etiology and pathologic mechanism underlying Alzheimer's disease (AD) are not clear. This study determined the effects of tau on amyloid-beta peptide(Aβ)-induced synaptic damages in a Drosophila model of AD.Galactose-regulated upstream promoter element 4(Gal4) and an upstream active sequence system was used to establish four kinds of Aβ transgenic Drosophila models of AD. Behavioral evaluation and immunohistochemical localization were performed in Aβ transgenic Drosophila models. Tau mutants were introduced into arctic mutant Aβ1-42 (arctic mutant Aβ [Aβarc]) Drosophila. The P{Gal4}A307 Drosophila strain was used as a control group; 12 strains were obtained to determine the effects of tau with or without Aβarc. Electrophysiologic records of the tau mutant groups were created.The flight and crawling ability of Aβ transgenic Drosophila were gradually weakened compared to the control group, and the life span was significantly shorter than the control group. Aβ was specifically expressed in the Drosophila giant fiber pathway and further accumulated in neuronal cell bodies based on immunohistochemistry. The percentage of the excitatory junctional potential (EJP) response in transgenic Drosophila expressing Aβarc was significantly decreased, which was approximately 40% lower than the control group. The tau deletion mutation alleviated the synaptic transmission disorder caused by Aβ and improved the viability of Drosophila.The tau deletion mutation significantly improved the synaptic damage caused by Aβ, and tau protein played an indispensable role in the synaptic dysfunction caused by Aβ, suggesting that Aβ and tau have close interactions in the pathogenesis of AD.

Efr3 is a newly identified plasma membrane protein and plays an important role in the phosphoinositide metabolism on the plasma membrane. However, although it is highly expressed in the brain, the functional significance of Efr3 in the brain is not clear. In the present study, we generated