Alzheimer Disease ; diagnosis ; genetics ; Genetic Testing ; Humans ; Predictive Value of Tests

To evaluate the differential diagnostic role of apolipoprotein E (apoE) genotype in dementia, we carried out a meta- analysis of 78 case-control series, including our own new data. The dementia subjects were grouped into Alzheimer's disease (AD) and non-AD. AD patients were subgrouped according to their subtypes, and non-AD patients into vascular dementia (VD), mixed dementia (MD), and non-AD non-VD dementia (NAVD). The apoE allele frequencies and apoE genotype-specific odds ratio (OR) of each group were estimated. The (4 allele frequency was higher in all of the dementia subgroups than in the elderly controls, and the associations with (4 allele were lower in the non-AD (OR 1.8) patients than in the AD (OR 4.2) patients. However, the apoE-related risk alsovaried as a function of the subgroup, in both the AD and non-AD groups; for AD, it was dependent on the subtype of AD (OR 2.3 - 11.3), and higher in late- onset and familial cases than in early-onset and sporadic cases, respectively; among non-AD patients, it was higher in MD (OR 2.6) than in VD (OR 1.3), and intermediate in NAVD (OR 1.9), in which a significant difference was also found between Lewy body dementia (LBD) type (OR 5.1) and non-LBD type (OR 1.3). In conclusion, variability in the apoE-related risk was found in both the AD and non-AD cases, depending on the subgroup. Therefore, precise subgrouping of both AD and non-AD patients should be performed, and this information should taken into consideration when interpreting the results of apoE genotyping.
Aged ; Aged, 80 and over ; Alzheimer Disease/diagnosis/genetics ; Apolipoproteins E/*genetics ; Dementia/*diagnosis/*genetics ; Dementia, Vascular/diagnosis/genetics ; Diagnosis, Differential ; Female ; Genotype ; Human ; Male ; Middle Aged

OBJECTIVEMutations of presenilin 1 (PSEN1) gene are the most frequent cause for familial Alzheimers disease (AD). This study was set to explore potential mutation of PSEN1 gene in a Chinese family featuring early-onset Alzheimers disease (FAD).

METHODSDNA was isolated from peripheral blood samples from 17 members of the FAD family as well as 10 patients with sporadic Alzheimers disease and 100 healthy subjects. With polymerase chain reaction (PCR) and Sanger sequencing, exons 113 of the PSEN1 gene were analyzed.

RESULTSDNA sequencing has revealed a heterozygous point mutation from G to A at position 1133 (Gly378Glu) of exon 11 of PSEN1 gene in 6 members from the family, among whom 5 were patients with dementia, whilst the remaining 1 was clinically normal but under onset age. The same mutation was not found in all other patients and the normal controls.

CONCLUSIONA novel missense mutation of the PSEN1 gene, Gly378Glu, probably underlies the autosomal dominant early-onset FAD in this Chinese family.

Adult ; Aged ; Alzheimer Disease ; diagnosis ; genetics ; Base Sequence ; Female ; Humans ; Male ; Middle Aged ; Pedigree ; Presenilin-1 ; genetics

Adult ; Alzheimer Disease ; diagnosis ; diagnostic imaging ; genetics ; Family Health ; Female ; Humans ; Male ; Pedigree ; Positron-Emission Tomography ; methods

Alzheimer's disease (AD) is an increasing epidemic threatening public health. Both men and women are susceptible to the disease although women are at a slightly higher risk. The prevalence of AD rises exponentially in elderly people from 1% at age of 65 to approximately 40%-50% by the age of 95. While the cause of the disease has not been fully understood, genetics plays a role in the onset of the disease. Mutations in three genes (APP, PSEN1, and PSEN2) have been found to cause AD and APOE4 allele increases the risk of the disease. As human genomic research progresses, more genes have been identified and linked with AD. Genetic screening tests for persons at high risk of AD are currently available and may help them as well as their families better prepare for a later life with AD.
Aged ; Aged, 80 and over ; Aging ; genetics ; metabolism ; Alzheimer Disease ; diagnosis ; epidemiology ; genetics ; Amyloid beta-Protein Precursor ; genetics ; metabolism ; Apolipoprotein E4 ; genetics ; Genetic Predisposition to Disease ; genetics ; Genetic Testing ; trends ; Humans ; Mutation ; genetics ; Presenilins ; genetics ; metabolism ; Risk Factors

Alzheimer's disease (AD) is an age-related, progressive neurodegenerative disorder that occurs gradually and results in memory, behavior, and personality changes. Abnormal sphingolipid metabolism was reported in AD previously. This study aimed to investigate whether sphK1 could exacerbate the accumulation of amyloid protein (Aβ) and sharpen the learning and memory ability of the animal model of AD using siRNA interference. An adenovirus vector expressing small interfering RNA (siRNA) against the sphK1 gene (sphK1-siRNA) was designed, and the effects of sphK1-siRNA on the APP/PS1 mouse four weeks after treatment with sphK1-siRNA hippocampal injection were examined. SphK1 protein expression was confirmed by using Western blotting and ceramide content coupled with S1P secretion was evaluated by enzyme-linked immunosorbent assay (ELISA). Aβ load was detected by immunohistochemical staining and ELISA. Morris water maze was adopted to test the learning and memory ability of the APP/PS1 mice. A significant difference in the expression of sphK1 protein and mRNA was observed between the siRNA group and the control group. Aβ load in transfected mice was accelerated in vivo, with significant aggravation of the learning and memory ability. The sphK1 gene modulation in the Aβ load and the learning and memory ability in the animal model of AD may be important for the treatment of AD.
Alzheimer Disease ; diagnosis ; physiopathology ; therapy ; Animals ; Disease Models, Animal ; Gene Silencing ; Genetic Therapy ; methods ; Learning Disorders ; diagnosis ; physiopathology ; therapy ; Mice ; Mice, Transgenic ; Microinjections ; Phosphotransferases (Alcohol Group Acceptor) ; genetics ; RNA, Small Interfering ; administration & dosage ; genetics ; therapeutic use ; Treatment Outcome