Expression Of Alzheimer's Disease Research Articles

Brain Infarction and the Clinical Expression of Alzheimer Disease

Brain Infarction and the Clinical Expression of Alzheimer Disease

Age-related changes in the expression of Alzheimer's beta APP in the brain of senescence accelerated mouse (SAM)-P/10.

Patients with Alzheimer's disease (AD) show loss of memory and cognitive deficits the molecular mechanisms of which are not completely known. We examined age-related changes in the expression levels of beta-amyloid precursor protein (beta APP) in the brain of the senescence accelerated mouse (SAM) P/10, which shows age-dependent brain atrophy and impairment in learning and memory, and in the senescence resistant mouse (SAM)-R/1 using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Levels of both beta APP mRNA and protein increased with age, reaching a peak at 8 months of age in the hippocampus of SAM-P/10. In contrast, beta APP protein level decreased with age in the hippocampus of SAM-R/1 while beta APP mRNA level did not change significantly. Levels of beta APP mRNA and protein showed no change with ageing in other brain regions, including cerebral cortex, thalamus/midbrain and cerebellum brain stem. These results suggest that the beta APP over-expression in the hippocampus might be related to the characteristic memory loss in SAM-P/10.

Expression of Alzheimer's amyloid precursor protein in human lymphocyte.

Beta-amyloid precursor protein (betaAPP) has been shown to be involved in cell growth regulation. In spleen, the majority of cells showing betaAPP like immunoreactivity was found in the T cell-dependent zone. In Northern blot, the expression of betaAPP was increased to reach the peak at 72 h after the treatment of phytohemagglutinin (PHA). But, in cytofluorometry, almost all CD4(+) T helper/inducer cells and the majority of CD(8+) T suppressor/cytotoxic cells show betaAPP immunoreactivity which remained constant during the stimulation with PHA. These results suggest that betaAPP is a surface molecule of T lymphocyte and the turnover or release of APP might be increased with the treatment of T cell mitogen.

444 Expression of Alzheimer's disease associated genes in vitro and in vivo using viral vectors

444 Expression of Alzheimer's disease associated genes in vitro and in vivo using viral vectors

Discovery of a brain promoter from the human transferrin gene and its utilization for development of transgenic mice that express human apolipoprotein E alleles.

Transgenic mice carrying heterologous genes directed by a 670-bp segment of the regulatory sequence from the human transferrin (TF) gene demonstrated high expression in brain. Mice carrying the chimeric 0.67kbTF-CAT gene expressed TF-CAT in neurons and glial cells of the nucleus basalis, the cerebrum, corpus callosum, cerebellum, and hippocampus. In brains from two independent TF-CAT transgenic founder lines, copy number of TF-CAT mRNA exceeded the number of mRNA transcripts encoding either mouse endogenous transferrin or mouse endogenous amyloid precursor protein. In two transgenic founder lines, the chloramphenicol acetyltransferase (CAT) protein synthesized from the TF-CAT mRNA was estimated to be 0.10-0.15% of the total soluble proteins of the brain. High expression observed in brain indicates that the 0.67kbTF promoter is a promising director of brain expression of heterologous genes. Therefore, the promoter has been used to express the three common human apolipoprotein E (apoE) alleles in transgenic mouse brains. The apoE alleles have been implicated in the expression of Alzheimer disease, and the human apoE isoforms are reported to interact with different affinities to the brain beta-amyloid and tau protein in vitro. Results of this study demonstrate high expression and production of human apoE proteins in transgenic mouse brains. The model may be used to characterize the interaction of human apoE isoforms with other brain proteins and provide information helpful in designing therapeutic strategies for Alzheimer disease.

Nonclassical roles of cholinesterases in the embryonic brain and possible links to Alzheimer disease.

Evidence about nonclassic functions of acetyl- (AChE) and butyryl-cholinesterase (BChE) during embryonic development of vertebrate brains is compared with evidence of their expression in Alzheimer disease (AD). Before axons extend in the early neural tube, BChE expression shortly precedes the expression of AChE. BChE is associated with neuronal and glial cell proliferation, and it may also regulate AChE. AChE is suggested to guide and stabilize growing axons. Pathologically, cholinesterase expression in AD shows some resemblance to that in the embryo. These findings are inconsistent with the "cholinergic hypothesis." Rather, it is suggested that cholinesterases in AD function nonclassically as in the embryo, possibly as part of a "neoembryonic" restorative program. These views may open new strategies for pharmacology and therapy for AD.

Impairment in mitochondrial cytochrome oxidase gene expression in Alzheimer disease

Brains from 5 patients with Alzheimer's disease (AD) showed a 50%–65% decrease in mRNA levels of the mitochondrial-encoded cytochrome oxidase (COX, a marker of oxidative metabolism) subunits I and III in the middle temporal association neocortex, but not in the primary motor cortex, as compared to 5 control brains. The amount of mitochondrial-encoded 12S rRNA was not altered, nor was the amount of nuclear-encoded lactate dehydrogenase B mRNA (a marker of glycolytic metabolism). These data suggest that the decrease in COX I and III subunits mRNA in affected brain regions may contribute to reduced brain oxidative metabolism in AD.

Apolipoprotein E is a relevant susceptibility gene that affects the rate of expression of Alzheimer's disease

Apolipoprotein E is a relevant susceptibility gene that affects the rate of expression of Alzheimer's disease

Purification of a Trypsin-Type Protease from Human Umbilical Vein Endothelial Cells Which Is Highly Sensitive to the Kunitz Inhibitor Domain Peptide of Alzheimer’s Disease Amyloid Protein Precursor

A trypsin-type protease was purified to enzymatic homogeneity from human umbilical vein endothelial cells by sequential affinity chromatographies. The enzyme specifically hydrolyzed dibasic substrates with leucine at the P3 positions, but scarcely hydrolyzed the other substrates tested. The enzyme was strongly inhibited by the Kunitz inhibitor domain peptide of Alzheimer's disease amyloid protein precursor (Ki value, 0.35 nM) and by the microbial inhibitors leupeptin and anti-pain. These results, together with a previous finding of a significant increase in the expression of Alzheimer's amyloid protein precursors (beta APPs) with the Kunitz inhibitor domain in Alzheimer's disease, suggest that the activity of the trypsin-type protease is suppressed by an increase of beta APPs with inhibitor activity in Alzheimer's disease, resulting in aberrant intracellular protein catabolism including degradation of beta APPs and beta-protein deposition.

Structure and expression of Alzheimer's disease amyloid protein precursor gene

Structure and expression of Alzheimer's disease amyloid protein precursor gene

Expression of Alzheimer's disease amyloid precursor protein during post-natal development of rat brain : ∗E. Milward 1, R. Martins 1, B. Rumble 1, R. Moir 1, A. Weidemann 2, K. Beyreuther 2, C. Masters 1. Department of Pathology, University of Melbourne and Mental Health Institute of Victoria, Royal Park Hospital, Parkville, Vic., 3052, Australia 1 and Center for Molecular Biology,

Expression of Alzheimer's disease amyloid precursor protein during post-natal development of rat brain : ∗E. Milward 1, R. Martins 1, B. Rumble 1, R. Moir 1, A. Weidemann 2, K. Beyreuther 2, C. Masters 1. Department of Pathology, University of Melbourne and Mental Health Institute of Victoria, Royal Park Hospital, Parkville, Vic., 3052, Australia 1 and Center for Molecular Biology,