1 Periodic Variation Of Aak1 In An Ab_1-42-Induced Mouse Model Of Alzheimer's Disease 2 Chinese Version Of The Baylor Profound Mental Status Examination

Aim:Inhibition of endocytosis in an Alzheimer's disease(AD)model has been shown to be able to prevent amyloid ?(Ap)-induced damage and to exert a beneficial effect in treating AD.Adaptor associated kinase 1(AAK1),which binds to the adaptor protein complex 2(AP-2),regulates the process of clathrin-mediated endocytosis.However,how AAK1 expression varies over the course of AD is unknown.Methods:A?1-42 was used to establish a mouse AD model,and the Morris water maze test was used to characterize the time course of A?1-42-induced cognition changes.ELISA was used to determine AAK1 levels in plasma and A?1-42 levels in brain tissues.Subsequently,the protein or gene levels of AAK1,AP-2 and Rab5(an early endosome marker)were tested in each group.Results:The cognitive function of A?1-42-induced mice was significantly declined compared to control group,and the deficits reached a peak on day 14,but partly recovered on day 30.Moreover,the level of A?1-42 detected with ELISA was highest on day 14,but reduced on day 30,paralleling the cognitive changes in the mice in our study.AAK1,AP-2 and Rab5 expression showed the same periodic variation as the changes in cognition.Thus,periodic variation in AAK1 expression is closely correlated to the decline in cognition.Conclusions:AAK1 expression is closely correlated to the decline in cognition,AAK1 might be a suitable indicator for AD and AAK1 might be a potential target for AD treatment.Background:A specialized instrument for assessing the cognition of patients in the severe stage of Alzheimer's disease(AD)is needed.Aim:To validate the Chinese version of the Baylor Profound Mental Status Examination(BPMSE-Ch).Methods:The Baylor Profound Mental Status Examination(BPMSE)was translated into Chinese and back translated.The BPMSE-Ch was administered to 102 AD patients with a Mini-Mental State Examination(MMSE)score below 17.We assessed the internal consistency,reliability(inter-rater reliability and test-retest reliability),and construct validity between the BPMSE-Ch and MMSE,Severe Impairment Battery(SIB),Global Deterioration Scale(GDS'),Geriatric Depression Scale(GDS2),Instrumental Activities of Daily Living(IADL),Physical Self-Maintenance Scale(PSMS),Neuropsychiatric Inventory(NPI)and Clinical Dementia Rating(CDR).Results:The BPMSE-Ch showed good internal consistency(? = 0.87);and inter-rater and test-retest reliability were both excellent,ranging from 0.91 to 0.99(p<0.001).The construct validity of the measure was also supported by significant correlations with MMSE,SIB,GDS1,IADL,PSMS,NPI and CDR(p<0.001).Moreover,as expected,the BMPSE-Ch had a lower floor effect than the MMSE,but a ceiling effect existed for patients with MMSE scores above 11.Conclusions:The BPMSE-Ch is a reliable and valid tool for evaluating cognitive function in patients with severe AD.