BACKGROUND: Apolipoprotein E (ApoE) gene polymorphism is associated with the onset of Alzheimer disease (AD), most of the researchers reported that ApoE ε4 allele accounts for familial AD as well as for sporadic AD.OBJECTIVE: This study was designed to validate the relationship between ApoE gene polymorphism and the sporadic AD in Aged Adults in Urumqi, and to evaluate the value of ApoE gene for prediction the risk of sporadic AD.DESIGN: Controlled comparative study based on patients.SETTING: It was conducted at the Institute of Clinical Medicine and the Neurological Department of Urumqi General Hospital of Lanzhou Military Area Command of Chinese PLA.PARTICIPANTS: From January 2001 to January 2003, 60 aged inpatients and outpatients at the Neurological Department of Urumqi General Hospital of Lanzhou Military Area Command of Chinese PLA and elderly in the Old People's Home were screened for AD. Of all these participants,28 were males and 32 were females, with an age from 52 to 91, in average of (74.2±19.5) years old, They had 0-16 years education, in average of 4.43 years, 28 were illiterate, 13 were at primary school educational level,12 were at junior middle school educational level, 4 were at high school educational level and 3 were at college educational level. From February to December 2002, 90 genetically unrelated individuals with healthy physical examination findings in Xinjiang area were selected into control group, 59males and 31 females, with an age from 50 to 101 years old, in average of (69.9±25.5) years old, have 0-16 year's education, in average of 7.96years. Of all the controls, 14 were illiterate, 23 were at primary educational level, 25 were at junior middle school educational level, 21 were at high school educational level and 7 were at college educational level. Informed consents were obtained from all the participants.METHODS: 5 Ml blood samples, anticoagulated with ethylene diamine tetraacetic acid (EDTA), were drawn from each participant. Then genome DNA was extracted from peripheral white blood cells using the phenolchloroform method. A fragment containing polymorphism site in exon 4 of ApoE were amplified using the polymerase chain reaction (PCR), were digested with Hha I and were identified using electrophoresis and silver staining. Then, ApoE genotypes and the frequency of ApoE alleles were compared between AD group and control group.MAIN OUTCOME MEASURES: ① ApoE genotypes and the frequency of ApoE alleles were measured in AD group and control group. ② The frequency of ApoE alleles were calculated in participants with different sex,age and educational level in AD group and control group.RESULTS: Sixty patients with AD and 90 healthy individuals participated this investigation. All of them entered the statistical analysis procedure.① The frequency of ε3/ε4 and ε4/ε4 alleles was higher in AD group than in control group (26.67%,11.11%; 3.33%, 1.11%; P ＜ 0.05). The frequency of e2/ε3 in AD group were lower than control group (5.00%,14.00%, P ＜0.05). ② The frequency of ApoE ε4 allele were higher in AD group as compared with control group (17.50%, 7.22%, P ＜ 0.05). The frequency of ApoE ε2 allele were lower in AD group (6.67%, 13.33%, P ＜ 0.05). ③ The frequency of ApoE ε4 allele in females were higher in AD group than in control group (20.97%, 5.00%, P ＜ 0.01). ④ In AD group, patients ≥ 75 years old have a lower frequency of ApoE ε4 allele compared to those less than 75 years (8.57%, 30.00%, P ＜ 0.01). And in individuals less than 75 years old, the frequency of ApoE ε4 allele were higher in AD group than that in control group (30.00%, 7.02%, P ＜ 0.01). ⑤ In illiterate persons and the individuals with only primary school educational level, the frequency of ApoE ε4 allele were higher in AD group than that in control group (10.00%, 0.56%, P ＜ 0.001; 5.00%,1.12%, P ＜ 0.01).CONCLUSION: ① It is proved that ApoE ε4 allele is significantly associated with sporadicAD in Urumqi and ε3/ε4 is the major genotype. ② ApoE ε2 allele has a protective effect on onset of AD. ③ Those individuals，female,less than 75,lower educational level or carrying ApoE ε4 allele take a higher risk of AD.

Objective To investigate the neuroprotective effect of Benztropine on retinal ganglion cells (RGCs) death and optic nerve injury in rats model of non-arteritis anterior ischemic optic neuropathy (rNAION).Methods A total of 25 Sprague-Dawley rats were randomly divided into Benztropine treatment group (n=13)and PBS control group (n=12).The right eye was set as the experimental eye.rNAION model was established by using rose Bengal combined with laser photodynamic method.The rats in the Benztropine treatment group were received intraperitoneal injection with Benztropine 10 mg/kg (0.2 ml) daily for 3 weeks,while the rats in the PBS control group were received intraperitoneal injection with an equal volume of PBS.At 1,3 and 7 days after modeling,the retinal and optic disc conditions of the rats were observed by direct ophthalmoscopy.Retrograde labeling,fluorescence microscopy and transmission electron microscopy were used to observe the survival of RGCs and the damage of the optic nerve myelin and axon at 4 weeks after modeling.The RGCs density and survival rate of the two groups were compared by One-Way Anova.Results At 1 and 3 days after modeling,the optic disc edema was observed in the rats of rNAION model group.At 7 days after modeling,the optic disc edema decreased and the boundary was blurred compared with 3 days after modeling.After 4 weeks,the RGCs density in the PBS group was 308± 194/mm2 and the survival rate was 13.7％.The density of RGCs in the Benztropine group was 1173+868/mm2 and the survival rate was 47.6％.The differences of RGCs density and survival rate were significant between the two groups (F=7.552,8.184;P=0.015,0.012).Myelin disintegration,axon degeneration,onion-like body and gliosis were observed in the optic nerve sections of rNIAON in the PBS group,while the damage ofaxon and myelin structure in the Benztropine group was significantly less than that in the PBS group.Conclusions Benztropine group showed higher RGC survival rate,less damage ofaxon and myelin structure on rNAION model.This study explored the potential neuroprotective effect of Benztropine.