Genetic Association between Akt1 Polymorphisms and Alzheimer's Disease in a Japanese Population

A recent paper reported that Aβ oligomer causes neuronal cell death through the phosphatidylinositol-3-OH kinase (PI3K)-Akt-mTOR signaling pathway. Intraneuronal Aβ, a main pathological finding of Alzheimer's disease (AD), is also known as inhibiting activation of Akt. This study aims to investigate whether single nucleotide polymorphisms (SNPs) of the Akt1 gene are associated with AD. SNPs genotyped using TaqMan technology was analyzed using a case-control study design. Our case-control dataset consisted of 180 AD patients and 130 age-matched controls. Although two SNPs showed superficial positive, Hardy-Weinberg equilibrium (HWE) tests, and linkage disequilibrium (LD) analyses suggested that genetic regions of the gene are highly polymorphic. We failed to detect any synergetic association among Akt1 polymorphisms, Apolipoprotein E (APO E), and AD. Further genetic studies are needed to clarify the relationship between the Akt1 and AD

Age-Related Association between Apolipoprotein E ε4 and Cognitive Function in Japanese Patients with Alzheimer's Disease

Aims: In the present study, we investigated whether apolipoprotein E (APOE) polymorphisms influenced the cognitive function of Japanese patients with Alzheimer's disease (AD) at certain ages. Methods: Among 200 outpatients with dementia and amnestic mild cognitive impairment, 133 Japanese patients with AD were recruited and divided into two genotypic groups: APOE ε4 carriers and noncarriers. Then, we compared several neuropsychological test scores between the two genotypic groups for two different generations: 70s (70-79 years) and 80s (80-89 years). Results: The total Mini-Mental State Examination score (p Conclusion: The present results suggest that APOE may significantly influence comparatively simple memory processing in certain generations of Japanese patients with AD

Lack of Genetic Associations of PPAR-γ and PGC-1α with Alzheimer's Disease and Parkinson's Disease with Dementia

Background and Aims: Similar clinical and pathological features have been observed in Alzheimer's disease (AD) and Parkinson's disease with dementia (PDD). Both the peroxisome proliferator-activated receptor-γ (PPAR-γ) gene and the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) gene are candidates modifying the risk for both diseases. The aim of this study was to clarify whether common single nucleotide polymorphisms (SNPs) of the PPAR-γ gene and the PGC-1α gene affect the onset of AD and PDD genetically. Methods: Four exonic SNPs of both genes (rs1801282 and rs3856806 of the PPAR-γ gene, rs3736265 and rs8192678 of the PGC-1α gene) were genotyped in 171 AD patients, 136 age-matched controls and 53 PDD patients. Haplotype analysis and logistic regression analysis with apolipoprotein E (APO E) status were performed for AD. Results: There was no statistical difference between AD cases and controls for the 4 SNPs, nor was there any statistical difference between PDD cases and controls for the 4 SNPs. We could not find any synergetic associations between these SNPs, APO E4 and AD. Conclusions: The 4 SNPs studied here did not influence the risk for AD in a Japanese population. As the number of PDD cases was small, comprehensive genetic studies considering diabetes would be needed

Genetic Association between Neurotrophin-3 Polymorphisms and Alzheimer's Disease in Japanese Patients

Background: Some polymorphisms of the neurotrophin family have previously been investigated as candidate genes for Alzheimer's disease (AD). In the present study, we examined whether neurotrophin-3 (NTF-3) polymorphisms are genetic risk factors in patients with AD. Methods: From a sample of 507 subjects, we recruited 248 age-matched subjects divided into 2 groups: AD patients (n = 143) and normal controls (NCs) (n = 105). We identified 3 representative NTF-3 single nucleotide polymorphisms (SNPs): rs6332, rs6489630, and rs4930767. Next, we statistically compared the allele frequencies of each SNP between the AD and NC groups in the early-onset (Results: We found a significant association between rs6332 and the total group of AD patients (p = 0.013) and significant associations between both rs6332 (p = 0.033) and rs6489630 (p = 0.035) and early-onset AD patients. Conclusion: These results suggest that NTF-3 SNPs may not only be associated with AD itself, but also with early-onset AD in Japanese patients, assuming that the NTF-3 gene may have age-related effects on neurodegenerative diseases

Association between DNA Methylation of the BDNF Promoter Region and Clinical Presentation in Alzheimer's Disease

Background/Aims: In the present study, we examined whether DNA methylation of the brain-derived neurotrophic factor (BDNF) promoter is associated with the manifestation and clinical presentation of Alzheimer's disease (AD). Methods: Of 20 patients with AD and 20 age-matched normal controls (NCs), the DNA methylation of the BDNF promoter (measured using peripheral blood samples) was completely analyzed in 12 patients with AD and 6 NCs. The resulting methylation levels were compared statistically. Next, we investigated the correlation between the DNA methylation levels and the clinical presentation of AD. Results: The total methylation ratio (in %) of the 20 CpG sites was significantly higher in the AD patients (5.08 ± 5.52%) than in the NCs (2.09 ± 0.81%; p Conclusion: These results suggest that the DNA methylation of the BDNF promoter may significantly influence the manifestation of AD and might be associated with its neurocognitive presentation

Association between DNA Methylation of the BDNF Promoter Region and Clinical Presentation in Alzheimer's Disease

Background/Aims: In the present study, we examined whether DNA methylation of the brain-derived neurotrophic factor (BDNF) promoter is associated with the manifestation and clinical presentation of Alzheimer's disease (AD). Methods: Of 20 patients with AD and 20 age-matched normal controls (NCs), the DNA methylation of the BDNF promoter (measured using peripheral blood samples) was completely analyzed in 12 patients with AD and 6 NCs. The resulting methylation levels were compared statistically. Next, we investigated the correlation between the DNA methylation levels and the clinical presentation of AD. Results: The total methylation ratio (in %) of the 20 CpG sites was significantly higher in the AD patients (5.08 ± 5.52%) than in the NCs (2.09 ± 0.81%; p Conclusion: These results suggest that the DNA methylation of the BDNF promoter may significantly influence the manifestation of AD and might be associated with its neurocognitive presentation