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1. Chitinase-1 Enhances The Microglia TGFβ-Smad Signaling Pathway And The Phagocytosis Of β Amyloid; 2. Analysis Of The Incidence Of Mental And Behavioral Symptoms In Patients With Cognitive Impairment In Memory Impairment Clinics

Posted on:2019-04-14Degree:MasterType:Thesis
Country:ChinaCandidate:X WangFull Text:PDF
GTID:2434330566982217Subject:Geriatrics
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Objective:TGFβ-Smad signaling,which is involved in modulation of P-amyloid(AP)clearance in microglia,is impaired in Alzheimer’s disease(AD)brains.Chitotriosidase(CHIT1)is elevated in AD,and has been reported to augment TGFβ signaling in fibroblast and T cells.We investigated the role of CHIT1 on TGFβ-Smad signaling and Aβphagocytosis in N9 microglia.Methods:N9 Microglial cell cultures were treated with TGFβ1 and CHIT1,alone or in combination,with or without pretreatment with the TGFβ receptors Ⅰ(Tβ Ⅰ)inhibitor.The mRNA levels of TβRI were detected by qRT-PCR.The protein levels of TβRI,Smad2/3,pSmad2/3 were detected by Western blot.And Aβ uptake were visualized by confocal microscope.Results:TGFβ1 treatment resulted in increased expression of TβRI,pSmad2/3,and uptake of Aβ compared to the control group.CHIT1 itself had no effect on the expression of TβRI,pSmad2/3,and uptake of Aβ.However,co-treatment with CHIT1 and TGFβ1 resulted in significant increased expression of TPRI,pSmad2/3,and uptake of Aβ compared to TGFβ1 treatment alone,which were inhibited by pretreatment with TβRI inhibitor.The levels of total Smad2/3 were not altered by different treatments.Conclusion:CHIT 1 may play a protective role in Aβ clearance via the enhancement of TGFβ-Smad signaling in microglia.Objective:To investigate the prevalence of neuropsychiatric symptoms in patients with mild cognitive impairment(MCI)and Alzheimer’s disease(AD)from the memory clinic of The First Affiliated Hospital of Chongqing Medical University.Methods:We selected patients who attended the memory clinic of The First Affiliated Hospital of Chongqing Medical University.Patients and their caregivers underwent neuropsychological examinations,and the demographics of all patients were recorded.Neuropsychiatric symptoms(NPSs)were assessed by the Neuropsychiatric Inventory(NPI),and Clinical Dementia Rating(CDR)was used to classify the severity of AD.Results:169 patients with MCI and 308 patients with AD(192 were classified as mild,84 as moderate,and 32 as severe)were included in this study.49.1%of patients with MCI,79.7%of patients with mild AD,96.4%of patients with moderate AD,and 100.0%of patients with severe AD exhibited one or more NPSs.The prevalence of delusions,hallucinations,anxiety,apathy,irritability,and aberrant motor activity in mild AD were significant higher than that in MCI group(χ2=19.448,7.873,12.386,11.756,7.743,13.390,all P<0.0167).The prevalence of all symptoms in moderate AD group were significant higher than that in mild AD group except for irritability(all P<0.0167).The prevalence of aberrant motor activity,sleep disturbance,and disinhibition in severe AD group were significant higher than that in moderate AD group(χ2=17.673,9.995,16.987,all P<0.0167).There was no statistically significance in NPSs between women and men in MCI patients(P>0.05).However,in AD patients,the prevalence of delusions and depression in women were significant higher than that in men(χ2=8.609,23.560,both P<0.05).Conclusion:The prevalence and severity of NPSs gradually increase following cognitive impairment increased.Women with AD are more prone to have delusions and depression than men.
Keywords/Search Tags:chitotriosidase, TGFβ1, microglia, Smad signaling, β-amyloid, memory clinic, mild cognitive impairment, Alzheimer’s disease, Neuropsychiatric symptoms
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