Search results for "Alzheimer disease"
showing 10 items of 428 documents
Genistein effect on cognition in prodromal Alzheimer's disease patients : the GENIAL clinical trial
2022
Background: Delaying the transition from minimal cognitive impairment to Alzheimer’s dementia is a major concern in Alzheimer’s disease (AD) therapeutics. Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet efective substances are recommended. There is a need to develop new drugs to delay Alzheimer’s dementia. We have taken a nutritional supplement approach with genistein, a chemically defned polyphenol that acts by multimodal specifc mechanisms. Our group previously showed that genistein supplementation is efective to treat the double transgenic (APP/PS1) AD animal model. Methods: In this…
Gradient-echo and CRAZED imaging for minute detection of Alzheimer plaques in an APPV717I x ADAM10-dn mouse model.
2007
Different strategies to visualize amyloid plaques with MRI at 17.6 Tesla were investigated in a novel mouse model of Alzheimer's disease (AD). Large iron-containing plaques were observed in the thalamus, but cortical plaques did not show iron deposits. Plaques in the thalamus were visualized in vivo with the use of low-resolution, 3D gradient-echo (GRE) imaging in 82 s, and with 94-microm resolution in 34 min. The feasibility of obtaining bright contrast from plaques using the COSY revamped with asymmetric z-GRE detection (CRAZED) technique was investigated in experiments on fixed brains. The original CRAZED approach provided reduced signal near the plaques (similarly to GRE imaging) and ad…
Cellular Prion Protein Participates in Amyloid-β Transcytosis across the Blood—Brain Barrier
2012
The blood—brain barrier (BBB) facilitates amyloid-β (Aβ) exchange between the blood and the brain. Here, we found that the cellular prion protein (PrPc), a putative receptor implicated in mediating Aβ neurotoxicity in Alzheimer's disease (AD), participates in Aβ transcytosis across the BBB. Using an in vitro BBB model, [125I]-Aβ1–40 transcytosis was reduced by genetic knockout of PrPc or after addition of a competing PrPc-specific antibody. Furthermore, we provide evidence that PrPc is expressed in endothelial cells and, that monomeric Aβ1–40 binds to PrPc. These observations provide new mechanistic insights into the role of PrPc in AD.
The sea urchin embryo: a model to study Alzheimer's beta amyloid induced toxicity.
2009
Abstract Alzheimer’s disease (AD) is the most common form of dementia. The cause of AD is closely related to the accumulation of amyloid beta peptide in the neuritic plaques. The use of animal model systems represents a good strategy to elucidate the molecular mechanism behind the development of this pathology. Here we use the Paracentrotus lividus embryo to identify molecules and pathways that can be involved in the degenerative process. As a first step, we identified the presence of an antigen related to the human APP, called Pl APP. This antigen, after gastrula stage, is processed producing a polypeptide of about 10 kDa. By immunohistochemistry we localized the Pl APP antigen in some ser…
In vitro fibrillogenesis of the amyloid beta 1-42 peptide: cholesterol potentiation and aspirin inhibition.
2002
Understanding the formation of extracellular amyloid neurofibrillar bundles/senile plaques and their role in the development of Alzheimer's disease is of considerable interest to neuroscientists and clinicians. Major components of the extracellular neurofibrillar bundles are polymerized amyloid beta (Abeta) peptides (1-40), (1-42) and (1-43), derived in vivo from the soluble amyloid precursor protein (sAPP) by proteolytic (beta- and gamma-secretase) cleavage. The Abeta(1-42) peptide is widely considered to be of greatest significance in relation to the pathogenesis of Alzheimer's disease. A well-defined ultrastructural characteristic within Alzheimer dense plaques is the presence of helical…
Detection of Amyloid-β Fibrils Using Track-Etched Nanopores: Effect of Geometry and Crowding
2021
Several neurodegenerative diseases have been linked to proteins or peptides that are prone to aggregate in different brain regions. Aggregation of amyloid-β (Aβ) peptides is recognized as the main cause of Alzheimer's disease (AD) progression, leading to the formation of toxic Aβ oligomers and amyloid fibrils. The molecular mechanism of Aβ aggregation is complex and still not fully understood. Nanopore technology provides a new way to obtain kinetic and morphological aspects of Aβ aggregation at a single-molecule scale without labeling by detecting the electrochemical signal of the peptides when they pass through the hole. Here, we investigate the influence of nanoscale geometry (conical an…
Synthesis and evaluation of 18F-fluoroethylated benzothiazole derivatives for in vivo imaging of amyloid plaques in Alzheimer's disease
2010
Amyloid aggregates play a major role in the development of Alzheimer's disease. Targeting these aggregates by PET probes enables non-invasively the detection and quantification of amyloid deposit distribution in human brains. Based on benzothiazole core structure a series of amyloid imaging agents were developed. Currently [(11)C]2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole (Pittsburgh Compound-B (PIB) is the most specific and widely used amyloid imaging ligand. But due to the short half life of (11)C, longer lived (18)F-labeled derivatives offer logistic advantages and higher contrast images. In this work, three different [(18)F]fluoroethoxy-substituted benzothiazole derivatives ([(18…
Antioxidant Pathways in Alzheimers Disease: Possibilities of Intervention
2011
Alzheimer's disease (AD) is closely related to the occurrence of oxidative stress. It was claimed that all pathophysiological mechanisms involved in the onset and progression of AD are related to oxidative stress. Thus, it is important to evaluate if there is oxidative stress as well as the mechanism by which this happens in AD patients as well as in animal models of AD. Extracellular plaques of amyloid b peptides (Aβ), a hallmark of the disease, have been postulated to be more protective than damaging in terms of oxidative stress because they may be chemical sinks in which heavy metals are placed. More than a decade ago we reasoned that damage due to Ab might be caused not by extracellular…
Metabolite profile and in vitro activities of Phagnalon saxatile (L.) Cass. relevant to treatment of Alzheimer’s disease
2009
The present study describes for the first time the in vitro properties (inhibition of NO production and anticholinesterase) of Phagnalon saxatile (L.) Cass. (Asteraceae). The methanolic extract showed antioxidant activity that was measured by DPPH assay and beta-carotene bleaching test. The same extract inhibited NO production in the murine monocytic macrophage cell line RAW 264.7. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition was assessed by modifications of Ellman's method. Purification of the MeOH extract of P. saxatile allowed the isolation of phenolic compounds. Among them, the compounds that most effectively inhibited lipopolysaccharide-induced NO production …
Reductive stress in young healthy individuals at risk of Alzheimer disease.
2013
Oxidative stress is a hallmark of Alzheimer disease (AD) but this has not been studied in young healthy persons at risk of the disease. Carrying an Apo e4 allele is the major genetic risk factor for AD. We have observed that lymphocytes from young, healthy persons carrying at least one Apo e4 allele suffer from reductive rather than oxidative stress, i.e., lower oxidized glutathione and P-p38 levels and higher expression of enzymes involved in antioxidant defense, such as glutamylcysteinyl ligase and glutathione peroxidase. In contrast, in the full-blown disease, the situation is reversed and oxidative stress occurs, probably because of the exhaustion of the antioxidant mechanisms just ment…