Search results for "ALZHEIMER"
showing 10 items of 706 documents
Transcriptomic and Genetic Associations between Alzheimer's Disease, Parkinson's Disease, and Cancer.
2021
Simple Summary Epidemiological studies have identified a link between neurodegenerative disorders and a reduced risk of overall cancer. Increases and decreases in the risk of site-specific cancers have also been reported. However, it is still unknown whether these associations arise due to shared genetic and molecular factors or are explained by other phenomena (e.g., biases in epidemiological studies or the use of medication). In this study, we aimed to investigate the potential molecular, genetic, and pharmacological links between Alzheimer’s and Parkinson’s diseases and a large panel of 22 cancer types. To examine the overlapping involvement of genes and pathways, we obtained differentia…
Serum Levels of Clusterin, PKR, and RAGE Correlate with Amyloid Burden in Alzheimer's Disease.
2021
Background: Alzheimer’s disease (AD) is the most common form of dementia and biomarkers are essential to help in the diagnosis of this disease. Image techniques and cerebrospinal fluid (CSF) biomarkers are limited in their use because they are expensive or invasive. Thus, the search for blood-borne biomarkers is becoming central to the medical community. Objective: The main objective of this study is the evaluation of three serum proteins as potential biomarkers in AD patients. Methods: We recruited 27 healthy controls, 19 mild cognitive impairment patients, and 17 AD patients. Using the recent A/T/N classification we split our population into two groups (AD and control). We used ELISA kits…
Oxidative signature of cerebrospinal fluid from mild cognitive impairment and Alzheimer disease patients
2015
Abstract Background Several studies suggest that pathological changes in Alzheimer’s disease (AD) brain begin around 10–20 years before the onset of cognitive impairment. Biomarkers that can support early diagnosis and predict development of dementia would, therefore, be crucial for patient care and evaluation of drug efficacy. Although cerebrospinal fluid (CSF) levels of Aβ42, tau, and p-tau are well-established diagnostic biomarkers of AD, there is an urgent need to identify additional molecular alterations of neuronal function that can be evaluated at the systemic level. Objectives This study was focused on the analysis of oxidative stress-related modifications of the CSF proteome, from …
Standardized measurement of circulating vitamin D [25(OH)D] and its putative role as a serum biomarker in Alzheimer's disease and Parkinson's disease
2019
The current review provides an overview on the development of 25(OH)D measurement standardization tools over the last three decades and clarifies whether there is a role as a serum biomarker for vitamin D in neurological diseases. In the past, a lack of internationally recognized 25(OH)D reference measurement procedures and reference standard materials led to unstandardized serum total 25(OH)D results among research and clinical care laboratories. The vitamin D Standardization Program (VDSP) has been introduced in 2010 to address this problem, however, vitamin D External Quality Assessment Scheme (DEQAS) reports still show substantial sample- to- sample variability. Further, immunoassays, w…
Mice are not Men: ADAM30 Findings Emphasize a Broader Look Towards Murine Alzheimer's Disease Models
2016
Due to the growing population of people at advanced age, the number of patients affected by Alzheimer's disease (AD) is increasing tremendously. In 2015 about 46.8 million people suffered from AD worldwide which is estimated to increase to 131.5 million by 2050. Brains of AD patients all show a common histopathology; they are marked by an atrophy and degeneration that is caused by a severe loss of neurons and synapses (Braak and Del Tredici, 2012). Moreover, so-called extracellular senile plaques that consist of predominantly amyloid β (Aβ) peptides can be detected in the grey matter where they surround neurons. Since generation of Aβ peptides is hypothesized to play a major role in AD path…
Reductive Stress: A New Concept in Alzheimer's Disease
2015
Reactive oxygen species play a physiological role in cell signaling and also a pathological role in diseases, when antioxidant defenses are overwhelmed causing oxidative stress. However, in this review we will focus on reductive stress that may be defined as a pathophysiological situation in which the cell becomes more reduced than in the normal, resting state. This may occur in hypoxia and also in several diseases in which a small but persistent generation of oxidants results in a hormetic overexpression of antioxidant enzymes that leads to a reduction in cell compartments. This is the case of Alzheimer's disease. Individuals at high risk of Alzheimer's (because they carry the ApoE4 allele…
Amyloid in Alzheimer’s Disease: Guilty Beyond Reasonable Doubt?
2017
Recently failed antiamyloidogenic trials call for an objective reassessment of the dominating amyloid cascade hypothesis of Alzheimer's disease (AD). Ongoing efforts focusing on amyloid β protein (Aβ), its deposition, and its removal need to be complemented by more intensive research in new directions. Those may either integrate amyloid pathology or will propose pathogenetic routes independent of Aβ in the search for the causes of AD.
Identification of Phlogacantholide C as a Novel ADAM10 Enhancer from Traditional Chinese Medicinal Plants
2016
Background: Alzheimer’s disease is one of the most prevalent dementias in the elderly population with increasing numbers of patients. One pivotal hallmark of this disorder is the deposition of protein aggregates stemming from neurotoxic amyloid-beta peptides. Synthesis of those peptides has been efficiently prevented in AD model mice by activation of an enzyme called alpha-secretase. Therefore, drugs with the capability to increase the expression of this enzyme, named ADAM10, have been suggested as a valuable therapeutic medication. Methods: We investigated 69 substances from a drug library derived from traditional Chinese medicine by luciferase reporter assay in human neuronal cells for th…
PTEN recruitment controls synaptic and cognitive function in Alzheimer's models
2016
Dyshomeostasis of amyloid-β peptide (Aβ) is responsible for synaptic malfunctions leading to cognitive deficits ranging from mild impairment to full-blown dementia in Alzheimer's disease. Aβ appears to skew synaptic plasticity events toward depression. We found that inhibition of PTEN, a lipid phosphatase that is essential to long-term depression, rescued normal synaptic function and cognition in cellular and animal models of Alzheimer's disease. Conversely, transgenic mice that overexpressed PTEN displayed synaptic depression that mimicked and occluded Aβ-induced depression. Mechanistically, Aβ triggers a PDZ-dependent recruitment of PTEN into the postsynaptic compartment. Using a PTEN kno…
Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer's disease.
2017
Alzheimer's disease (AD) is the most prevalent form of dementia. The exact pathophysiology of this disease remains incompletely understood and safe and effective therapies are required. AD is highly correlated with neuroinflammation and oxidative stress in brain causing neuronal loss. Nuclear factor of activated B-cells (NF-κB) is involved in physiological inflammatory processes and thus representing a promising target for inflammation-based AD therapy. Phytochemicals are able to interfere with the NF-κB pathway. They inhibit the phosphorylation or the ubiquitination of signaling molecules, and thus, inhibit the degradation of IκB. The translocation of NF-κB to the nucleus and subsequent tr…