With the intensification of population aging， the proportion of people with dementia in our country is rising sharply， bringing a heavy economic and caregiving burden to families and society. Alzheimer's disease （AD） is a spectrum of progressive cognitive impairment disorders that onset in old age， characterized by memory decline， reduced attention and executive function， and in the late stages of the disease， it can even progress to dementia， ultimately leading to the loss of self-care abilities and further increasing the pressure on families and society. Patients with Alzheimer's disease （AD） can be in a preclinical stage for decades without obvious clinical cognitive decline， but significant pathological changes have already occurred in the brain， including the aggregation of beta-amyloid （Aβ） to form senile plaques， the hyperphosphorylation and aggregation of tau protein to form neurofibrillary tangles， vascular amyloid deposition， synaptic and neuronal loss， as well as neuroinflammation. This stage represents the best opportunity for early intervention in AD. Accurate diagnosis or prediction of AD risk and implementation of intervention measures can significantly delay or prevent the progression of AD. In recent years， the application of various tracers that track the neuropathological changes of AD in PET/CT has led to significant progress in clinical research on the imaging diagnosis， treatment monitoring， and prognostic prediction of preclinical and early-stage AD. This article will review the application of PET/CT and PET/MR techniques marked with Aβ， tau protein， fluorodeoxyglucose （FDG）， synaptic， and inflammatory tracers in the early diagnosis， differential diagnosis， disease staging， treatment monitoring， and prognostic prediction of AD， and compare the relative utility and limitations of these tracers as biomarkers， providing a basis and reference for clinicians to choose appropriate PET markers in the research of early diagnosis and treatment of preclinical AD and early-stage AD.

To explore whether the downregulation of protein phosphatase 2A catalytic subunit(PP2Ac)involved in the pathogenesis of mitochondria fission/fusion dynamics and functional imbalance induced by human tau accumulation. After cotransfection with mito-dsRed plasmids and pIRES-eGFP-tau40 plasmids 48 hours,the rat primary hippocampal neurons were observed with a laser scanning confocal microscope for their changes in shape and distribution of mitochondria.The expressions of mitochondria fission/fusion protein and PP2Ac and PP2Ab were detected by Western blotting.Furthermore,the shape and distribution of mitochondria of rat primary hippocampal neuron and wild type 293wt cells were assayed 48 hours after co-transfection with siPP2Ac-EGFP plasmids and mito-DsRed plasmids,and the fission/fusion dynamics of 293wt cells was captured with live cell time-lapse imaging after co-transfection with siPP2Ac plasmids and mito-Dendra2 plasmids.After transfection with siPP2Ac plasmids,the relative level of mitochondria fission/fusion protein of 293wt cells was assayed by Western blotting,and mitochondria membrane potential was detected by JC-1 staining,and the cellular viability was measured by CCK8 assay.Finally,the shape and distribution and membrane potential of mitochondria of HEK293 cells with stable transfection of htau40(293htau)were detected after co-transfection with PP2Ac and mito-dsRed plasmids. Human tau40 expression decreased distribution of mitochondria and significantly lowered PP2Ac level in primary hippocampal neuron(=4.814, =0.0086).Down-regulation of PP2Ac caused mitochondria elongation and perinuclear accumulation in primary hippocampal neuron and 293wt cells;in addition,down-regulation of PP2Ac in 293wt cells significantly increased mitochondria fusion rate(=2.857, =0.0074)and the levels of mitochondria fusion protein mitofusin(MFN)1(=6.768, =0.0025),MFN2(=3.121, =0.0035),and optic atrophy 1(=3.775, =0.0199);however,the levels of dynamin-like protein-1 and Fis1 remained unchanged.The down-regulation of PP2Ac in 293wt cells led to the significant decrease in mitochondria membrane potential(=2.300, =0.0270)and cell viability(=6.249, <0.0001).Finally,up-regulation of PP2Ac attenuated the abnormalities in the shape,distribution and function of mitochondria in the 293htau cells. Down-regulation of PP2Ac is involved in the abnormal shape and distribution of mitochondria and its dysfunction induced by human tau40 in rat primary hippocampal neurons and HEK293 cells.
Animals ; Catalytic Domain ; Down-Regulation ; HEK293 Cells ; Humans ; Mitochondria ; Protein Phosphatase 2 ; Rats ; tau Proteins

AIM:To explore the preventive effect of resveratrol on spatial memory loss of the mice induced by intralateroventricular injection of calyculin A (CA).METHODS:Kunming mice of 2 months (n=44) were divided into saline control group, CA group, low-dose resveratrol group and high-dose resveratrol group.The mice in control group and CA group were intraperitoneally injected with equal volume of saline for 21 d, while the mice in low-dose resveratrol group and high-dose resveratrol group were intraperitoneally injected with resveratrol at 5 mg/kg and 10 mg/kg, respectively.At 22 d, CA (4 μL) was injected into the lateral ventricles in CA group, low-dose resveratrol group and high-dose resveratrol group.Morris water maze test was applied to examine the changes of learning and memory abilities of the mice at 27 d.The Golgi staining was used to observe the morphological changes of dendrites and dendritic spines.The hippocampal tissues were homogenated to detect SOD activity.RESULTS:Low-dose resveratrol significantly decreased the escape latency delay induced by CA.Low-dose resveratrol attenuated the decreases in the number of dendrites and the density of dendritic spines of neurons in hippocampal CA1 region induced by CA.High-dose resveratrol but not low-dose resveratrol attenuated the decreased SOD activity induced by CA.CONCLUSION:Resveratrol at low dose attenuates memory loss in the mice induced by CA though preventing dendrite injury.

AIM:To investigate the protective effects of astrocyte protein phosphatase 2A (PP2A) up-regula-tion on APP/PS1 double transgenic mice.METHODS:An eGFP-wtPP2A lentivirus with glial fiber acidic protein promoter was constructed to specifically increase PP2A expression in the astrocytes.The mice were divided into wild -type mice +vector virus group (Con), APP/PS1 transgenic mice +vector virus group (APP/PS1) and APP/PS1 transgenic mice +eGFP-wtPP2A lentivirus group (PP2A) by lateral ventricular injection of the lentivirus.Four weeks after injection of the vi-rus, the immunofluorescence of brain slices were used to detect the level of β-amyloid protein ( Aβ) .Golgi staining was used to detect the changes of dendritic spine density and morphology.Electron microscopy was applied to detect the thickness of postsynaptic density (PSD).The Morris water maze test was applied to examine the learning and memory abilities of the mice.RESULTS: Up-regulation of PP2A in the astrocytes attenuated Aβlevel increasing in APP/PS1 group.Up-regulation of PP2A in the astrocytes significantly attenuated both decreases in the dendritic spine density and the percentage of mushroom-like dendritic spines in the hippocampal CA3 region of APP/PS1 mice.Up-regulation of PP2A in the astrocytes significantly attenuated the reduced thickness of PSD in APP/PS1 group.Up-regulation of PP2A in the astro-cytes attenuated the escape latency extending in APP/PS1 group .CONCLUSION: Up-regulation of PP2A in the astro-cytes reduces AD-like pathological changes, and attenuates synaptic impairment, synaptic plasticity deficits and cognitive impairment in the APP/PS1 double transgenic mice.

Teaching and Research Section of Pathophysiology of Medical School of Three Gorges University explored the methods to cultivate innovative thinking of university student. These methods included inspiring potential of innovative thinking by pathophysiology development rule , get-ting rid of regular psychological tendency by clinical case and introducing innovative thinking training method by medical innovation case. These experiences may provide references for innovative education.

Objective To investigate the in vivo effect of melatonin(Mel) on calyculin A(CA)-induced tau hyperphosphorylation in neuroblastoma cells(N2awt).Methods We treated N2awt cells with CA or CA and 50 ?mol/L Mel,detected the level of tau phosphorylation with immunofluorescence,and assayed the activities of GSK3 and the ratio of GSK-3? phosphorylated at Ser9 site to total GSK-3?.Results CA treatment led to tau hyperphosphorylation accompanied with the increased activity of GSK-3 and the decreased ratio of GSK-3? phosphorylated at Ser9 site to total GSK-3?.When the cells were incubated simultaneously with CA and 50 ?mol/L Mel,the CA-induced tau hyperphosphorylation,GSK-3 activation and the ratio of GSK-3? phosphorylated at Ser9 site to total GSK-3? decrease were attenuated.Conclusion Melatonin protects neuroblastoma cells from CA-induced tau hyperphosphorylation.Its protection may be related to the regulation of GSK-3 activity and the ratio of GSK-3? phosphorylated at Ser9 site to total GSK-3? increase.

Objective To investigate the in vivo effect of melatonin on calyculin A-induced neurofilament(NF) hyperphosphorylation in neuroblastma cells(N2awt).Methods N2awt cells were treated with CA or CA and different concentration melatonin or CA and vitamin E,the levels of neurofilament phosphorylation and the level of PP-2A were detected,and the activities of PP-2A were assayed.Results Calyculin A treatment led to neurofilament hyperphosphorylation by decreasing the level and activity of PP-2A.Both melatonin and vitamin E had protective effect on calyculin A-induced neurofilament hyperphosphorylation,although melatonin increased the activity of PP-2A while vitamin E did not.Morever,melatonin partially attenuated the decreasing of PP-2A level. Conclusion Melatonin protects neuroblastma cells from CA-induced neurofilament hyperphosphorylation through the regulation of PP-2A level and the increase of PP-2A activity.