Objective To determine the association between the polymorphism of angiotensin converting enzyme (ACE) gene and Alzheimer's disease (AD). Methods This case-control study involved 201 AD patients and 257 healthy subjects matched for age and gender as the control group. Polymerase chain reaction amplification and matrix-assisted laser desorption/ionization time of flight mass spectrometry were used to examine the rs4291, rs4309, and rs4343 of ACE gene, and the difference in genotypes, allelotype frequencies and haplotype frequencies were analyzed between the two groups. Results No statistic difference was found in the genotype and allelotype frequencies of rs4291 locus between AD and control groups (P>0.05). A significant difference was found in the genotype and allelotype frequencies of rs4309 between the two groups with a significant increase in the C allelotype frequency in AD group (OR=1.917, 95% CI=1.431-2.568, P<0.05). The difference in the genotype frequency of rs4343 was not significant between the two groups, but the allelotype frequencies differed significantly with a decreased A allelotype frequency in AD group(OR=0.714, 95%CI=0.532-0.957, P=0.024). Analysis of the linkage disequilibrium among the loci of rs4291, rs4309 and rs4343 showed a D’all above 0.65 between one another. Haplotype analysis confirmed the existence of 5 haplotypes, namely ATA, ACA, TCA, TCG and TTG, indicating a negative correlation between haplotype ATA and AD occurrence (OR=0.558, 95% CI=0.420-0.741, P<0.05) and positive correlations of haplotype ACA and TCA with AD occurrence (ACA:OR=4.883, 95%CI=2.267-10.518, P<0.05;TCA:OR=2.269, 95%CI=1.083-4.754, P<0.05). Conclusion The polymorphism of rs4291 may have no relation with the incidence of AD. Polymorphisms of s4309 and rs4343 may be related to AD, and ATA, ACA and TCA haplotypes composed of rs4291/rs4309/rs4343 may be related to AD.

Objective To determine the association between the polymorphism of angiotensin converting enzyme (ACE) gene and Alzheimer's disease (AD). Methods This case-control study involved 201 AD patients and 257 healthy subjects matched for age and gender as the control group. Polymerase chain reaction amplification and matrix-assisted laser desorption/ionization time of flight mass spectrometry were used to examine the rs4291, rs4309, and rs4343 of ACE gene, and the difference in genotypes, allelotype frequencies and haplotype frequencies were analyzed between the two groups. Results No statistic difference was found in the genotype and allelotype frequencies of rs4291 locus between AD and control groups (P>0.05). A significant difference was found in the genotype and allelotype frequencies of rs4309 between the two groups with a significant increase in the C allelotype frequency in AD group (OR=1.917, 95% CI=1.431-2.568, P<0.05). The difference in the genotype frequency of rs4343 was not significant between the two groups, but the allelotype frequencies differed significantly with a decreased A allelotype frequency in AD group(OR=0.714, 95%CI=0.532-0.957, P=0.024). Analysis of the linkage disequilibrium among the loci of rs4291, rs4309 and rs4343 showed a D’all above 0.65 between one another. Haplotype analysis confirmed the existence of 5 haplotypes, namely ATA, ACA, TCA, TCG and TTG, indicating a negative correlation between haplotype ATA and AD occurrence (OR=0.558, 95% CI=0.420-0.741, P<0.05) and positive correlations of haplotype ACA and TCA with AD occurrence (ACA:OR=4.883, 95%CI=2.267-10.518, P<0.05;TCA:OR=2.269, 95%CI=1.083-4.754, P<0.05). Conclusion The polymorphism of rs4291 may have no relation with the incidence of AD. Polymorphisms of s4309 and rs4343 may be related to AD, and ATA, ACA and TCA haplotypes composed of rs4291/rs4309/rs4343 may be related to AD.

OBJECTIVETo observe the changes of miRNA expression profiles in APPswe/PSδE9 transgenic mice and explore the possible roles of miRNA in the pathogenesis of Alzheimer's disease.

METHODSUsing miRNA chip technique, we examined the miRNA expression in the brain tissue of 6-month-old APPswe/PSδE9 transgenic mice, with age-matched wild-type mice as the control group.

RESULTSTwelve miRNAs showed differential expressions by more than two folds in APPswe/PSδE9 transgenic mice, namely miRNA-135a, miRNA-135a-2*, miRNA-298, miRNA-466b-3p, miR-669-3p, miR-142-5p, miR-144, miR-466f-3p, miR-466g, miR-200a, miR-200b and miR-96. Five miRNAs were significantly down-regulated in the transgenic mice, including miRNA-135a, miRNA-135a-2*, miRNA-298, miRNA-466b-3p, and miR-669-3p.

CONCLUSIONThe 5 down- regulated miRNA may play important roles in the pathogenesis of AD in APPswe/PSδE9 transgenic mice.

Alzheimer Disease ; genetics ; metabolism ; Animals ; Disease Models, Animal ; Gene Expression Profiling ; Mice ; Mice, Transgenic ; MicroRNAs ; genetics ; metabolism ; Oligonucleotide Array Sequence Analysis ; Transcriptome

OBJECTIVETo detect the expression of miRNA-135a-5p, miRNA-135a-2-3p, miRNA-298-5p, miRNA-466b-3p and miR-669f-3p in the brain tissue of the APPswe/PS δE9 double transgenic mouse model of Alzheimer's disease using real-time PCR.

METHODSSix-month-old APPswe/PS δE9 double transgenic mice and wild-type C57 mice of the same species were examined for the expressions of miRNA-135a-5p, miRNA-135a-2-3p, miRNA-298-5p, miRNA-466b-3p and miR-669f-3p in the brain tissue using real-time PCR.

RESULTSThe relative expression levels of the 5 miRNAs in the transgenic versus the wild-type mice were 0.73∓0.27 vs 1.08∓0.58, 2.47∓6.15 vs 1.65∓0.67, 0.72∓0.14 vs 1.31∓0.73, 0.57∓0.34 vs 1.06∓0.35, and 0.63∓0.26 vs 1.02∓0.18, respectively, showing significance differences in the expressions of miRNA-135a-5p, miRNA-298-5p, miRNA-466b-3p, and miR-669f-3p between the two groups (P<0.05).

CONCLUSIONSmiRNA-135a-5p, miRNA-298-5p, miRNA-466b-3p and miR-669f-3p are expressed differentially in APPswe/PS δE9 double transgenic mice, suggesting their important roles in the pathogenesis of Alzheimer disease.

Alzheimer Disease ; genetics ; metabolism ; Animals ; Brain ; metabolism ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; MicroRNAs ; genetics ; metabolism ; Real-Time Polymerase Chain Reaction ; methods

OBJECTIVETo detect the expression of signal transducer and activator of transcription 3 (STAT3) and P-STAT3 in the brain of the APPswe/PS δE9 double transgenic mouse model of Alzhaimer's disease (AD) and investigate their possible role in AD.

METHODSAPPswe/PS δE9 double transgenic mice and control mice were examined for cerebral STAT3 and P-STAT3 expressions using immunothistochemistry.

RESULTSSTAT3 and P-STAT3 were expressed in the different regions of mouse brain. In the transgenic mice and the control mice, the positivity rates of STAT3 were 93.75% and 87.50% in the cerebral cortex, 87.50% and 43.75% in the basal forebrain, 81.25% and 37.50% in the hippocampus, and 62.50% and 0.00% in the cerebellum, respectively, showing significant differences between the mice in the STAT3 expressions in the basal forebrain, hippocampus and cerebellum (P<0.05). The positivity rates of P-STAT3 in the two groups were 0.00% and 0.00% in the cerebral cortex, 68.75% and 0.00% in the basal forebrain, 62.50% and 12.50% in the hippocampus, and 43.75% and 0.00% in the cerebellum, respectively, showing also significant differences in the basal forebrain, hippocampus and cerebellum (P<0.05). The expression of STAT3 was positively correlated with that of P-STAT3 in transgenic AD mice (P<0.05).

CONCLUSIONSTAT3 and P-STAT3 are highly expressed in the basal forebrain, hippocampus and cerebellum in transgenic AD mice and may participate in the pathological process of AD.

Alzheimer Disease ; metabolism ; Animals ; Cerebellum ; metabolism ; Cerebral Cortex ; metabolism ; Disease Models, Animal ; Hippocampus ; metabolism ; Mice ; Mice, Transgenic ; STAT3 Transcription Factor ; metabolism

OBJECTIVETo investigate the presence of β-amyloid peptide (Aβ) deposition in the cerebellum and the expression of related miRNAs in the cerebellum of a mouse model of Alzheimer disease.

METHODSTwelve 12-month-old APPswe/PSδE9 double transgenic mice and 12 wild-type C57 mice were sacrificed and the brain tissues were taken for examination. The right hemisphere was stained with Congo red to observe the deposition of amyloid substances, and from the left hemisphere, the hippocampus and the cerebellum were dissected for detecting the expression of miRNA-135a-5p, miRNA-298-5p, miRNA-466b-3p and miR-669f-3p using real-time PCR.

RESULTSCongo red staining revealed the presence of Aβ deposition in both the hippocampus and the cerebellum of the transgenic mice but not in the control mice. Real-time PCR showed a significantly lower expression of the 4 miRNAs in the hippocampus in the transgenic mice than in the control mice (P<0.05). The expression of miRNA-135a-5p, miRNA-298-5p, and miR-669f-3p in the cerebellum was significantly lower in the transgenic mice than in the control mice (P<0.05). The expression of miRNA-298-5p and miR-669f-3p in the hippocampus was significantly lower than that in the cerebellum of the transgenic mice (P<0.05).

CONCLUSIONβ deposition also occurs in the cerebellum of APPswe/PSδE9 double transgenic mice, and its formation might be related to the down-regulation of miRNA-135a-5p, miRNA-298-5p, and miR-669f-3p.

Alzheimer Disease ; metabolism ; Amyloid beta-Peptides ; metabolism ; Animals ; Cerebellum ; metabolism ; Disease Models, Animal ; Hippocampus ; metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; MicroRNAs ; metabolism

Objective To detect the expression of signal transducer and activator of transcription 3 (STAT3) and P-STAT3 in the brain of the APPswe/PS△E9 double transgenic mouse model of Alzhaimer's disease (AD) and invesitgate their possible role in AD. Methods APPswe/PS △E9 double transgenic mice and control mice were examined for cerebral STAT3 and P-STAT3 expressions using immunothistochemistry. Results STAT3 and P-STAT3 were expressed in the different regions of mouse brain. In the transgenic mice and the control mice, the positivity rates of STAT3 were 93.75%and 87.50%in the cerebral cortex, 87.50% and 43.75% in the basal forebrain, 81.25% and 37.50% in the hippocampus, and 62.50% and 0.00% in the cerebellum, respectively, showing significant differences between the mice in the STAT3 expressions in the basal forebrain, hippocampus and cerebellum (P<0.05). The positivity rates of P-STAT3 in the two groups were 0.00%and 0.00%in the cerebral cortex, 68.75%and 0.00% in the basal forebrain, 62.50% and 12.50% in the hippocampus, and 43.75% and 0.00% in the cerebellum, respectively, showing also significant differences in the basal forebrain, hippocampus and cerebellum (P<0.05). The expression of STAT3 was positively correlated with that of P-STAT3 in transgenic AD mice (P<0.05). Conclusion STAT3 and P-STAT3 are highly expressed in the basal forebrain, hippocampus and cerebellum in transgenic AD mice and may participate in the pathological process of AD.

Objective To investigate the presence of β-amyloid peptide (Aβ) deposition in the cerebellum and the expression of related miRNAs in the cerebellum of a mouse model of Alzheimer disease. Methods Twelve 12-month-old APPswe/PS△E9 double transgenic mice and 12 wild-type C57 mice were sacrificed and the brain tissues were taken for examination. The right hemisphere was stained with Congo red to observe the deposition of amyloid substances, and from the left hemisphere, the hippocampus and the cerebellum were dissected for detecting the expression of miRNA-135a-5p, miRNA-298-5p, miRNA-466b-3p and miR-669f-3p using real-time PCR. Results Congo red staining revealed the presence of Aβdeposition in both the hippocampus and the cerebellum of the transgenic mice but not in the control mice. Real-time PCR showed a significantly lower expression of the 4 miRNAs in the hippocampus in the transgenic mice than in the control mice (P<0.05). The expression of miRNA-135a-5p, miRNA-298-5p, and miR-669f-3p in the cerebellum was significantly lower in the transgenic mice than in the control mice (P<0.05). The expression of miRNA-298-5p and miR-669f-3p in the hippocampus was significantly lower than that in the cerebellum of the transgenic mice (P<0.05). Conclusion Aβdeposition also occurs in the cerebellum of APPswe/PS△E9 double transgenic mice, and its formation might be related to the down-regulation of miRNA-135a-5p, miRNA-298-5p, and miR-669f-3p.

Objective To investigate serum adiponectin level in patients with Alzheimer's disease (AD) and its correlation with the patients' cognitive function. Methods This case-control study was conducted in 90 patients with a highly probable diagnosis ofAD, who were divided into mild, moderate and severe group saccording to the MMSE score. Ninety healthy subjects matched for age and gender with the AD patients were selected as the control group. The serum levels ofadiponectin in the participants were detected using enzyme-linked immunosorbent assay. Results Serum adiponectin level was significantly lower in the AD group than in the control group (P<0.05). Of the 3 subgroups of the AD patients, the moderate and severe AD groups showed significantly lower serum adiponectin level sthan the control group (P<0.05), but the difference in adiponectin levels was not significant between the mild AD group and the control group (P>0.05);serum adiponectin levels also differed significantly among the 3 subgroups of AD patients (P<0.05). Serum adiponectin level was positively correlated with the MMSE score in the AD patients (r=0.683, P<0.001). Conclusion Serum adiponectin levels are reduced in AD patients and associated with the degree of cognitive impairment.

Objective To detect the expression of signal transducer and activator of transcription 3 (STAT3) and P-STAT3 in the brain of the APPswe/PS△E9 double transgenic mouse model of Alzhaimer's disease (AD) and invesitgate their possible role in AD. Methods APPswe/PS △E9 double transgenic mice and control mice were examined for cerebral STAT3 and P-STAT3 expressions using immunothistochemistry. Results STAT3 and P-STAT3 were expressed in the different regions of mouse brain. In the transgenic mice and the control mice, the positivity rates of STAT3 were 93.75%and 87.50%in the cerebral cortex, 87.50% and 43.75% in the basal forebrain, 81.25% and 37.50% in the hippocampus, and 62.50% and 0.00% in the cerebellum, respectively, showing significant differences between the mice in the STAT3 expressions in the basal forebrain, hippocampus and cerebellum (P<0.05). The positivity rates of P-STAT3 in the two groups were 0.00%and 0.00%in the cerebral cortex, 68.75%and 0.00% in the basal forebrain, 62.50% and 12.50% in the hippocampus, and 43.75% and 0.00% in the cerebellum, respectively, showing also significant differences in the basal forebrain, hippocampus and cerebellum (P<0.05). The expression of STAT3 was positively correlated with that of P-STAT3 in transgenic AD mice (P<0.05). Conclusion STAT3 and P-STAT3 are highly expressed in the basal forebrain, hippocampus and cerebellum in transgenic AD mice and may participate in the pathological process of AD.