BCHE
Cholinesterase precursor (EC 3.1.1.8) (Acylcholine acylhydrolase) (Butyrylcholine esterase) (Choline esterase II) (Pseudocholinesterase) [CHE1]
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The present study examined the influence of genetic polymorphisms in the apolipoprotein (APOE) and the butyrylcholinesterase (BCHE) gene on GC secretion, cognition and personality in 66 healthy older adults. These particular variables were chosen given that they have been shown to be associated with human stress (i.e.stress markers). Measures included basal serum GC levels and cognitive scores on declarative memory obtained annually over 3 years. Also, self-esteem, neuroticism and depression were evaluated. Results showed that participants with the APOE E4-BCHE K variant (E4-K group) present increased basal levels of GCs and poorer cognitive performance when compared to non-carriers of these variants. In addition, the E4-K group reported lower self-esteem and higher levels of depression. These findings may indicate a genotype effect on markers of stress and cognitive integrity years before symptoms of dementia are apparent.
MeSH Terms
- Aging
- Apolipoproteins E
- Biomarkers
- Butyrylcholinesterase
- Cognition
- Female
- Glucocorticoids
- Humans
- Longitudinal Studies
- Male
- Middle Aged
- Oxidative Stress
- Personality
- Polymorphism, Single Nucleotide
- Stress, Physiological
Alzheimer's disease is a genetically complex disorder associated with multiple genetic defects, either mutational or of susceptibility. Although potentially associated with an accelerated stochastically driven aging process, Alzheimer's disease is an independent clinical entity in which the aging process exerts a deleterious effect on brain activity in conjunction with polymodal genetic factors and other pathological conditions (i.e., age-related cerebrovascular deterioration) and environmental factors (i.e., nutrition). Alzheimer's disease genetics does not explain in full the etiopathogenesis of this disease. Therefore, it is likely that environmental factors and/or epigenetic phenomena also contribute to Alzheimer's disease pathology and phenotypic expression of dementia. The genomics of Alzheimer's disease is still in its infancy, but this field is aiding the understanding of novel aspects of this disease, including genetic epidemiology, multifactorial risk factors, pathogenic mechanisms associated with genetic networks and genetically regulated metabolic cascades. Alzheimer's disease genomics is also helping to develop new strategies in pharmacogenomic research and prevention. Functional genomics, proteomics, pharmacogenomics, high-throughput methods, combinatorial chemistry and modern bioinformatics will greatly contribute to accelerate drug development for Alzheimer's disease and other complex disorders. The multifactorial genetic dysfunction in dementia includes mutational loci (APP, PS1, PS2, TAU) and diverse susceptibility loci (APOE, alpha2M, alphaACT, LRP1, IL1 alpha, TNF, ACE, BACE, BCHE, CST3, MTHFR, GSK3 beta, NOS3 and many other genes) distributed across the human genome, probably converging in a common pathogenic mechanism that leads to premature neuronal death, in which mitochondrial DNA mutations may contribute to increased genetic variability and heterogeneity. In Alzheimer's disease, multiple pathogenic events, including genetic factors, accumulation of aberrant or misfolded proteins, protofibril formation, ubiquitin-proteasome system dysfunction, excitotoxic reactions, oxidative and nitrosative stress, mitochondrial injury, synaptic failure, altered metal homeostasis, dysfunction of axonal and dendritic transport, and chaperone misoperation may converge in pathogenic pathways leading to premature death and neurodegeneration. Some of these mechanisms are common to several neurodegenerative disorders, which differ depending upon the gene(s) affected and the involvement of specific genetic networks, together with epigenetic factors and environmental events. Many genes potentially associated with Alzheimer's disease in some studies cannot be confirmed as candidate genes in replication studies, indicating that methodological problems and genomic complexity are leading to erroneous conclusions. A different approach to Alzheimer's disease functional genomics is to integrate individual genetic information in polygenic genotypes (haplotype-like model) and to investigate genotype-phenotype correlations and genotype-related pharmacogenomic behaviors. The application of functional genomics to Alzheimer's disease can be a suitable strategy for molecular diagnosis and for understanding pathophysiological mechanisms associated with Alzheimer's disease-related neurodegeneration. Furthermore, the pharmacogenomics of Alzheimer's disease may contribute in the future to optimize drug development and therapeutics, increasing efficacy and safety, and reducing side-effects and unnecessary costs.
MeSH Terms
- Aging
- Alzheimer Disease
- Amyloid beta-Protein Precursor
- Animals
- Apolipoproteins E
- DNA, Mitochondrial
- Genetic Predisposition to Disease
- Genetic Testing
- Humans
- Membrane Proteins
- Molecular Chaperones
- Pharmacogenetics
- Presenilin-1
- Progeria
- Proteasome Endopeptidase Complex
- Risk Factors
- Sex Factors
- Ubiquitin-Protein Ligase Complexes
The association between the K-variant of the butyrylcholinesterase gene (BCHE-K) and Alzheimer disease (AD) or AD-related neuropathology has been reported to date with conflicting results. Here, we determined in a sample of 521 cases the severity of AD-related neuropathology and the polymorphisms of both BCHE-K and apolipoprotein E (ApoE). Histopathologically, all brains were classified according to procedures permitting differentiation of the evolutionary stages of neurofibrillary tangles (NFTs) and amyloid-beta-protein deposition (A beta-deposits). The results show that the association between BCHE-K and AD-related neuropathology only was limited to homozygotes for the K allele (P=0.036 for NFTs, and P=0.045 for A beta-deposits) at ages > or = 70 years but not 50-69 years. Furthermore, no interaction was apparent between BCHE-K and ApoE.
MeSH Terms
- Aged
- Aging
- Alzheimer Disease
- Apolipoproteins E
- Butyrylcholinesterase
- Cerebral Cortex
- DNA Mutational Analysis
- Female
- Gene Frequency
- Genetic Predisposition to Disease
- Genetic Testing
- Genotype
- Homozygote
- Humans
- Male
- Middle Aged
- Neurofibrillary Tangles
- Plaque, Amyloid
- Polymorphism, Genetic
{{medline-entry |title=Acetylcholinesterase and butyrylcholinesterase expression in adult rabbit tissues and during development. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/7925428 |abstract=A large cDNA fragment covering the complete sequence of the mature catalytic subunit of rabbit acetylcholinesterase (AChE) has been cloned and sequenced. This sequence was compared to that of rabbit butyrylcholinesterase [BChE; Jbilo, O.