Search results for "BETA-PROTEIN"
showing 10 items of 73 documents
Lack of APP and APLP2 in GABAergic Forebrain Neurons Impairs Synaptic Plasticity and Cognition.
2020
AbstractAmyloid-β precursor protein (APP) is central to the pathogenesis of Alzheimer’s disease, yet its physiological functions remain incompletely understood. Previous studies had indicated important synaptic functions of APP and the closely related homologue APLP2 in excitatory forebrain neurons for spine density, synaptic plasticity, and behavior. Here, we show that APP is also widely expressed in several interneuron subtypes, both in hippocampus and cortex. To address the functional role of APP in inhibitory neurons, we generated mice with a conditional APP/APLP2 double knockout (cDKO) in GABAergic forebrain neurons using DlxCre mice. These DlxCre cDKO mice exhibit cognitive deficits i…
Kinetics of Insulin Aggregation: Disentanglement of Amyloid Fibrillation from Large-Size Cluster Formation
2006
Kinetics of human insulin aggregation has been studied at pH 1.6 and 60 degrees C, when amyloid fibrils are formed. We developed a novel approach based on the analysis of scattered light intensity distribution, which allows distinguishing between small and large size aggregates. By this method, we observed an exponential growth of fibrillar aggregates implying a heterogeneous aggregation mechanism. Also, the apparent lag time observed, correlated with the major increase of thioflavin T fluorescence, has been assigned to the onset of large size cluster formation.
Reduced firing rates of pyramidal cells in the frontal cortex of APP/PS1 can be restored by acute treatment with levetiracetam
2020
Contains fulltext : 229488.pdf (Publisher’s version ) (Open Access) Contains fulltext : 229488pre.pdf (Author’s version preprint ) (Open Access) In recent years, aberrant neural oscillations in various cortical areas have emerged as a common physiological hallmark across mouse models of amyloid pathology and patients with Alzheimer's disease. However, much less is known about the underlying effect of amyloid pathology on single cell activity. Here, we used high-density silicon probe recordings from frontal cortex area of 9-month-old APP/PS1 mice to show that local field potential power in the theta and beta band is increased in transgenic animals, whereas single-cell firing rates, specifica…
Memory-enhancing and brain protein expression-stimulating effects of novel calcium antagonist in Alzheimer’s disease transgenic female mice
2016
The prevalence of Alzheimer's disease (AD) is higher in females than in males, and causes more severe cognitive, memory and behavioral impairments. Previously, in male transgenic (Tg) APPSweDI mice, we reported that the novel lipophilic 1,4-dihydropyridine (DHP) derivative AP-12 crossed the blood-brain barrier, blocked neuronal and vascular calcium channels, changed brain protein expression and improved behavior. In this study, we used female Tg APPSweDI mice to assess the effects of AP-12 on behavior, and brain protein expression, with a particular focus on those of the GABAergic system. The results showed that in female Tg mice, similar to male Tg mice, AP-12 improved spatial learning/mem…
Exercise and probiotics attenuate the development of Alzheimer's disease in transgenic mice: Role of microbiome
2018
Abstract It has been suggested that exercise training and probiotic supplementation could decelerate the progress of functional and biochemical deterioration in APP/PS1 transgenic mice (APP/PS1TG). APP/PS1TG mice were subjected to exercise training and probiotic treatments and functional, biochemical and microbiome markers were analyzed. Under these conditions the mice significantly outperformed controls on The Morris Maze Test, and the number of beta-amyloid plaques decreased in the hippocampus. B. thetaiotaomicron levels correlated highly with the results of the Morris Maze Test (p
Elevated Testosterone Level and Urine Scent Marking in Male 5xFAD Alzheimer Model Mice
2019
Background:Function of the Amyloid Precursor Protein (AβPP) and its various cleavage products still is not unraveled down to the last detail. While its role as a source of the neurotoxic Amyloid beta (Aβ) peptides in Alzheimer’s Disease (AD) is undisputed and its property as a cell attachment protein is intriguing, while functions outside the neuronal context are scarcely investigated. This is particularly noteworthy because AβPP has a ubiquitous expression profile and its longer isoforms, AβPP750 and 770, are found in various tissues outside the brain and in non-neuronal cells.Objective:Here, we aimed at analyzing the 5xFAD Alzheimer’s disease mouse model in regard to male sexual function.…
Loss of all three APP family members during development impairs synaptic function and plasticity, disrupts learning, and causes an autism-like phenot…
2021
The key role of APP for Alzheimer pathogenesis is well established. However, perinatal lethality of germline knockout mice lacking the entire APP family has so far precluded the analysis of its physiological functions for the developing and adult brain. Here, we generated conditional APP/APLP1/APLP2 triple KO (cTKO) mice lacking the APP family in excitatory forebrain neurons from embryonic day 11.5 onwards. NexCre cTKO mice showed altered brain morphology with agenesis of the corpus callosum and disrupted hippocampal lamination. Further, NexCre cTKOs revealed reduced basal synaptic transmission and drastically reduced long-term potentiation that was associated with reduced dendritic length …
Extract of Caragana sinica as a potential therapeutic option for increasing alpha-secretase gene expression
2015
Abstract Background Alzheimer's disease represents one of the main neurological disorders in the aging population. Treatment options so far are only of symptomatic nature and efforts in developing disease modifying drugs by targeting amyloid beta peptide-generating enzymes remain fruitless in the majority of human studies. During the last years, an alternative approach emerged to target the physiological alpha-secretase ADAM10, which is not only able to prevent formation of toxic amyloid beta peptides but also provides a neuroprotective fragment of the amyloid precursor protein – sAPPalpha. Purpose To identify novel alpha-secretase enhancers from a library of 313 extracts of medicinal plant…
Hereditary cerebral hemorrhage with amyloidosis associated with the E693K mutation of APP
2010
Objective To report the clinical, genetic, neuroimaging, and neuropathologic studies of patients with the hereditary cerebral hemorrhage with amyloidosis linked to the APP E693K mutation. Design Case series. Clinical details and laboratory results were collected by direct evaluation and previous medical records. DNA analysis was carried out in several affected subjects and healthy individuals. Neuropathologic examination was performed in 2 subjects. Setting Southern Lombardy, Italy. Patients Individuals with and without amyloidosis in 4 unrelated Italian families (N = 37). Main Outcome Measure Genotype-phenotype relationship. Results The affected individuals presented with recurrent headach…
A second family with familial AD and the V717L APP mutation has a later age at onset
2006
Four mutations have been reported at the 717 codon of the amyloid precursor protein (APP), with valine substituted by isoleucine, glycine, phenylalanine, and leucine. While several families with the isoleucine substitution have been described, the other substitutions have been reported in only one family each worldwide. A family with the V717L APP mutation has been previously reported,1 with a mean age at onset of 38 years (range 35 to 39), based on four affected family members, and a mean age at death of 46 years (range 40 to 50). We have identified a second family with a later mean age at onset of 50 years (range 48 to 57) and mean age at death of 61 years (range 57 to 68). Family 171 is …