Molecular and clinical insights into protein misfolding and associated amyloidosis.

Molecular and clinical insights into protein misfolding and associated amyloidosis. Eur J Med Chem. 2019 Oct 07;184:111753 Authors: Pande M, Srivastava R Abstract The misfolding of normally soluble proteins causes their aggregation and deposition in the tissues which disrupts the normal structure and function of the corresponding organs. The proteins with high β-sheet contents are more prone to form amyloids as they exhibit high propensity of self-aggregation. The self aggregated misfolded proteins act as template for further aggregation that leads to formation of protofilaments and eventually amyloid fibrils. More than 30 different types of proteins are known to be associated with amyloidosis related diseases. Several aspects of the amyloidogenic behavior of proteins remain elusive. The exact reason that causes misfolding of the protein and its association into amyloid fibrils is not known. These misfolded intermediates surpass the over engaged quality control system of the cell which clears the misfolded intermediates. This promotes the self-aggregation, accumulation and deposition of these misfolded species in the form of amyloids in the different parts of the body. The amyloid deposition can be localized as in Alzheimer disease or systemic as reported in most of the amyloidosis. The amyloidosis can be of acquired type or familial. The current review aims at bringing together recent updates and comprehensive information about protein amyloidosis ...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Tags: Eur J Med Chem Source Type: research

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C2N Diagnostics’s detection test for Alzheimer’s disease is showing off some strong data coming out of the 12th Annual Clinical Trials in Alzheimer’s Disease conference. The St. Louis-based company said results from a study show the Aptus-Aβ test strongly predicts the presence of brain amyloidosis in a diverse population. C2N Diagnostics said its blood-based in vitro diagnostic is being developed to predict amyloid PET scan results. It combines into a ratio, the concentration of amyloid beta (Aβ) isoforms Aβ42 and Aβ40 in ...
Source: MDDI - Category: Medical Devices Authors: Tags: IVD Source Type: news
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Nonphysiologic overexpression of amyloid-β (Aβ) precursor protein in common transgenic Aβ mouse models of Alzheimer disease likely hampers their translational potential. The novel AppNL-G-F mouse incorporates a mutated knock-in, potentially presenting an improved model of Alzheimer disease for Aβ-targeting treatment trials. We aimed to establish serial small-animal PET of amyloidosis and neuroinflammation in AppNL-G-F mice as a tool for therapy monitoring. Methods: AppNL-G-F mice (20 homozygous and 21 heterogeneous) and 12 age-matched wild-type mice were investigated longitudinally from 2.5 to 10 mo of ...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Basic Source Type: research
In conclusion, T2D impairs vascular function by dysregulated autophagy. Therefore, autophagy could be a potential target for overcoming diabetic microvascular complications. To What Degree Does Loss of Skeletal Muscle with Age Contribute to Immunosenescence? https://www.fightaging.org/archives/2019/11/to-what-degree-does-loss-of-skeletal-muscle-with-age-contribute-to-immunosenescence/ Sarcopenia, the progressive loss of muscle mass and strength, is characteristic of aging. A perhaps surprisingly large fraction of the losses can be averted by strength training, but there are nonetheless inexorable process...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we sought to assess the prevalence of AF in patients with clinically undetected isolated cardiac amyloidosis (ICA) detected at autopsy and identify electrocardiographic (EKG) markers of such amyloid deposits. A total of 1083 patients were included in the study and 3.1% of patients were found to have asymptomatic ICA. Patients with ICA were older and had a higher odds of AF independent of age and CHA2DS2VASc score. Amongst patients with AF, those with ICA were more likely to have persistent forms of AF and had a lower sinus rhythm P-wave amplitude. Further studies are required to further define this entity, i...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Epileptic activity without visible convulsions is common in Alzheimer's disease (AD) and may contribute adversely to the disease progress and symptoms. Transgenic mice with amyloid plaque pathology also display epileptic seizures, but those are too infrequent to assess the effect of anti-epileptic treatments. Besides spontaneous seizures, these mice also display frequent epileptic spiking in epidural EEG recordings, and these have provided a means to test potential drug treatment to AD-related epilepsy. However, the origin of EEG spikes in transgenic AD model mice has remained elusive, which makes it difficult to relate el...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
CONCLUSION: We propose that it is now necessary to consider whether neuroinflammation in Alzheimer's disease affects inflammation in the pancreas related to diabetes. PMID: 31692443 [PubMed - as supplied by publisher]
Source: Current Alzheimer Research - Category: Neurology Authors: Tags: Curr Alzheimer Res Source Type: research
We examined, in a community-based population (N = 777, aged 50-95) (1) what variables were associated with each of the CSF (N) markers, and (2) whether the variables associated with each marker differed by increased brain amyloid. CSF T-tau was measured with an automated electrochemiluminescence Elecsys immunoassay; NfL and Ng were measured with in-house enzyme-linked immunosorbent assays. RESULTS: Multiple variables were differentially associated with CSF NfL and T-tau levels, but not Ng. Most associations were attenuated after adjustment for age and sex. T-tau had the strongest association with cognition in...
Source: The Journal of Alzheimers Association - Category: Psychiatry Tags: Alzheimers Dement Source Type: research
Kinetic study of Aβ(1-42) amyloidosis in the presence of ganglioside-containing vesicles. Colloids Surf B Biointerfaces. 2019 Oct 31;185:110615 Authors: Dai Y, Zhang M, Shi X, Wang K, Gao G, Shen L, Sun T Abstract Alzheimer's disease (AD) is characterized by the amyloid-beta peptide (Aβ) misfolding to form aberrant amyloid aggregates in the brain. Although recent evidence implicates that amyloid deposition in vivo is highly related to biomembranes, how the characteristic lipid components of neuronal membranes mediate this process remains to be fully elucidated. Herein, we established vesicle...
Source: Colloids and Surfaces - Category: Biotechnology Authors: Tags: Colloids Surf B Biointerfaces Source Type: research
We examined, in a community-based population (N = 777, aged 50–95) (1) what variables were associated with each of the CSF (N) markers, and (2) whether the variables associated with each marker differed by increased brain amyloid. CSF T-tau was measured with an automated electrochemiluminescence Elecsys immunoassay; NfL and Ng were measured with in-house enzyme-linked immunosorbent assays.ResultsMultiple variables were differentially associated with CSF NfL and T-tau levels, but not Ng. Most associations were attenuated after adjustment for age and sex. T-tau had the strongest association with cognition in ...
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - Category: Geriatrics Source Type: research
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