Search results for "AMYLOID"
showing 10 items of 494 documents
Impact of Resilience on the Association Between Amyloid-β and Longitudinal Cognitive Decline in Cognitively Healthy Older Adults
2019
The present study aims at investigating if the association between amyloid-β and longitudinal cognitive decline in cognitively healthy elderly is modulated by resilience capacity. Resilience capacity was quantified by education, which is a common proxy of resilience and has been shown to be related to a wide range of behaviors promoting resilience. Analyses were conducted with longitudinal cognitive data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). 276 cognitively healthy older individuals (≥56 years) were included in the study. Baseline amyloid pathology was quantified using CSF amyloid-β 1-42 measurements. Longitudinal cognitive decline was assessed using ADAS13, Clinical …
Molecular properties underlying regional vulnerability to Alzheimer’s disease pathology
2018
Amyloid deposition and neurofibrillary degeneration in Alzheimer's disease specifically affect discrete neuronal systems, but the underlying mechanisms that render some brain regions more vulnerable to Alzheimer's disease pathology than others remain largely unknown. Here we studied molecular properties underlying these distinct regional vulnerabilities by analysing Alzheimer's disease-typical neuroimaging patterns of amyloid deposition and neurodegeneration in relation to regional gene expression profiles of the human brain. Graded patterns of brain-wide vulnerability to amyloid deposition and neurodegeneration in Alzheimer's disease were estimated by contrasting multimodal amyloid-sensiti…
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 …
18F-Florbetaben PET/CT to Assess Alzheimer's Disease: A new Analysis Method for Regional Amyloid Quantification.
2019
Background and purpose While AD can be definitively confirmed by postmortem histopathologic examination, in vivo imaging may improve the clinician's ability to identify AD at the earliest stage. The aim of the study was to test the performance of amyloid PET using new processing imaging algorithm for more precise diagnosis of AD. Methods Amyloid PET results using a new processing imaging algorithm (MRI-Less and AAL Atlas) were correlated with clinical, cognitive status, CSF analysis, and other imaging. The regional SUVR using the white matter of cerebellum as reference region and scores from clinical and cognitive tests were used to create ROC curves. Leave-one-out cross-validation was carr…
Altered insulin pathway compromises mitochondrial function and quality control both in in vitro and in vivo model systems.
2021
Abstract Altered insulin signaling and insulin resistance are considered the link between Alzheimer's disease (AD) and metabolic syndrome. Here, by using an in vitro and an in vivo model, we investigated the relationship between these disorders focusing on neuronal mitochondrial dysfunction and mitophagy. In vitro Aβ insult induced the opening of mitochondrial permeability transition pore (mPTP), mitochondrial membrane potential (ΔΨm) loss, and apoptosis while insulin addition ameliorated these dysfunctions. The same alterations were detected in a 16 weeks of age mouse model of diet-induced obesity and insulin resistance. In addition, we detected an increase of fission related proteins and …
Gender and age-dependent differences in the mitochondrial apoptogenic pathway in Alzheimer's disease
2008
Age-related mitochondrial oxidative stress is highly gender dependent. The aim of this study was to determine the role of gender in the mitochondrial contribution to neuronal apoptosis in Alzheimer's disease (AD). We used mitochondria isolated from brains of Wistar rats to study the toxicity of ss-amyloid peptide (Ass), and found that it increases mitochondrial peroxide production, nitration and oxidation of proteins, and release of cytochrome c. The toxic effects occurred in young males and in old females but not in young females, indicating their resistance to Ass. This resistance was abolished with age. These toxic effects of Ass were prevented by heme. Our findings provide a molecular m…
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…
Different electrophysiological actions of 24- and 72-hour aggregated amyloid-beta oligomers on hippocampal field population spike in both anesthetize…
2010
Diffusible oligomeric assemblies of the amyloid beta-protein (Abeta) could be the primary factor in the pathogenic pathway leading to Alzheimer's disease (AD). Converging lines of evidence support the notion that AD begins with subtle alterations in synaptic efficacy, prior to the occurrence of extensive neuronal degeneration. Recently, however, a shared or overlapping pathogenesis for AD and epileptic seizures occurred as aberrant neuronal hyperexcitability, as well as nonconvulsive seizure activity were found in several different APP transgenic mouse lines. This generated a renewed attention to the well-known comorbidity of AD and epilepsy and interest in how Abeta oligomers influence neu…
Senile amyloidosis: Principles of localization in a heterogeneous form of amyloidosis
1983
In order to identify amyloid deposits in patients over 60 years of age (so-called senile amyloid), the following five tissues were investigated under the light and electron microscope : 1. pituitary gland, 2. pancreatic islets of Langerhans, 3. heart, 4. aorta, and 5. brain. In all an increasing incidence of amyloid deposits was found with increasing age, and in the brain a significant quantitative increase in amyloid deposits with increasing age was observed. Despite the biochemical heterogeneity of amyloid found in old age, all the deposits seen in tissues examined were morphologically similar. Typical amyloid fibrils were always found (diameter 60–100 A), and these were invariably deposi…