Alzheimer Disease ; genetics ; metabolism ; therapy ; Humans ; tau Proteins ; genetics ; metabolism

MicroRNA are a group of non-coding RNA which, through regulating expression of proteins at post-transcription level, plays an important role in modulating growth and development of nervous system, cell differentiation and functions. Altered expression of microRNA in the brain may influence development and advance of Alzheimer's disease from multiple perspectives. Research on microRNA will facilitate in depth understanding of the pathogenesis of Alzheimer's disease.
Alzheimer Disease ; genetics ; metabolism ; Animals ; Humans ; MicroRNAs ; genetics ; metabolism

Humans ; Alzheimer Disease/genetics* ; Apolipoprotein E4/genetics* ; Amyloid beta-Peptides

Alzheimer's disease (AD) is the most common neurodegenerative disorder, which features mainly with memory impairment as the initial symptom of progressive loss of cognitive function. Its main pathological changes include senile plaques and neurofibrillary tangles. The pathogenesis of AD is still unclear, though it may be connected with aging, genetic factors and environmental factors. Among these, aging and environmental factors can be modified by epigenetics. In this paper, advances in the study of epigenetic mechanisms related to the pathogenesis of AD are reviewed.
Alzheimer Disease ; genetics ; psychology ; Animals ; Cognition ; Epigenesis, Genetic ; Humans

It is generally considered that various regulatory activities between genes are contained in the gene expression datasets. Therefore, the underlying gene regulatory relationship and the biologically useful information can be found by modeling the gene regulatory network from the gene expression data. In our study, two unsupervised matrix factorization methods, independent component analysis (ICA) and nonnegative matrix factorization (NMF), were proposed to identify significant genes and model the regulatory network using the microarray gene expression data of Alzheimer's disease (AD). By bio-molecular analyzing of the pathways, the differences between ICA and NMF have been explored and the fact, which the inflammatory reaction is one of the main pathological mechanisms of AD, is also emphasized. It was demonstrated that our study gave a novel and valuable method for the research of early detection and pathological mechanism, biomarkers' findings of AD.
Algorithms ; Alzheimer Disease ; genetics ; Gene Expression Profiling ; methods ; Humans

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

As the most common neurodegenerative disease, Alzheimer's disease (AD) is characterized by progressive cognitive decline and is a major threat to the health of elderly worldwide. Aside from its pathogenesis, delineation of the protective mechanism of AD is also critical for the etiological treatment. AD resilience refers to a protective mechanism which can maintain the cognitive intactness of patients despite of genetic risk factors and/or related pathology. Studies on the genetic mechanism of AD resilience are of great importance for revealing novel mechanisms and therapeutic targets, as well as optimizing polygenic risk score which can facilitate early identification and intervention for individuals at risk.
Aged ; Humans ; Alzheimer Disease/genetics* ; Neurodegenerative Diseases ; Cognitive Dysfunction

It is clear that organoids are useful for studying the structure as well as the functions of organs and tissues; they are able to simulate cell-to-cell interactions, symmetrical and asymmetric division, proliferation, and migration of different cell groups. Some progress has been made using brain organoids to elucidate the genetic basis of certain neurodevelopmental disorders. Such as Parkinson's disease and Alzheimer's disease. However, research on organoids in early neural development has received insufficient attention, especially that focusing on neural tube precursors. In this review, we focus on the recent research progress on neural tube organoids and discuss both their challenges and potential solutions.
Humans ; Organoids ; Neural Tube ; Neurodevelopmental Disorders/genetics* ; Brain ; Alzheimer Disease

OBJECTIVESTo formulate an equation for fine mapping of disease loci under complex conditions and determine the marker-disease distance in a specific case using this equation.

METHODSLewontin's linkage disequilibrium (LD) measure D' was used to formulate an equation for mapping disease genes in the presence of phenocopies, locus heterogeneity, gene-gene and gene-environment interactions, incomplete penetrance, uncertain liability and threshold, incomplete initial LD, natural selection, recurrent mutation, high disease allele frequency and unknown mode of inheritance. This equation was then used to determine the distance between a marker ( epsilon 4 within the apolipoprotein E gene, APOE) and Alzheimer's disease (AD) loci using published data.

RESULTSAn equation was formulated for mapping disease genes under the above conditions.If these conditions are present but ignored, then recombination fraction theta between marker and disease loci will be either overestimated or estimated with little bias. Therefore, an upper limit of theta can be obtained. AD has been found to be associated with the marker allele epsilon 4 in Africans, Asians, and Caucasians. This suggests that the AD- epsilon 4 allelic LD predates the divergence of peoples occurring 100 000 years ago. With the age of AD- epsilon 4 allelic LD so estimated, the maximal distance was calculated to be 23.2 kb (mean 5.8 kb).

CONCLUSIONS(1) A method is developed for LD mapping of susceptibility genes. (2) A mutation within the APOE gene itself, among others, is responsible for the susceptibility to AD, which is supported by recent evidence from studies using transgenic mice.

OBJECTIVETo investigate the correlation between the polymorphisms of apolipoprotein E(APOE), the interleukin-1 alpha (IL-1 alpha ) genes and the susceptibility to Alzheimer's disease(AD).

METHODSAssociation study was performed in 114 AD patients and 113 healthy elderly individuals from Chengdu, China. Polymorphisms of APOE and IL-1 alpha genes were analyzed with polymerase chain reaction-restriction fragment length polymorphism.

RESULTSThe frequency of APOE-epsilon 4-carrying genotype in moderate to severe AD patients (28.6%) was higher than that of mild patients (18.5%) and the controls (14.2%), and the difference between moderate to severe AD group and the control group was significant (OR=2.4, 95%CI: 1.1-5.5). The frequency of epsilon 4 was also of significant difference between the group of moderate to severe dementia and the control group (OR=2.6, 95%CI: 1.3-5.3). However, no significant difference in distribution of IL-1 alpha polymorphism between AD patients and controls was observed.

CONCLUSIONThe APOE epsilon 4 allele was associated with moderate to severe AD while no association between the IL-1 alpha gene polymorphism and AD was found.