Differential roles of plasma protein corona on immune cell association and cytokine secretion of oligomeric and fibrillar beta-amyloid.

In this study, the effects of the plasma protein corona have been investigated with regard to the blood cell association and cytokine secretion of oligomeric (Aβo) and fibrillar Aβ1-42 (Aβf), two major forms of the peptide aggregates. Aβo displayed little change in membrane association in whole blood or washed blood (i.e., cells in the absence of plasma proteins) at 37 ºC, while Aβf showed a clear preference for binding with all cell types sans plasma proteins. Immune cells exposed to Aβo, but not to Aβf, resulted in significant expression of cytokines IL-6 and TNF measured in real-time by a localized surface plasmon resonance sensor. These observations indicate greater immune cell association and cytokine stimulation of Aβo than Aβf, and shed new light on the contrasting toxicities of Aβo and Aβf resulting from their differential capacities in acquiring a plasma protein corona. These results further implicate a close connection between Aβ amyloidosis and immunopathology in AD. PMID: 31600059 [PubMed - as supplied by publisher]
Source: Biomacromolecules - Category: Biochemistry Authors: Tags: Biomacromolecules Source Type: research

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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
Researchers at the University of Turku have discovered new changes in blood samples associated with Alzheimer’s disease. A new study was conducted on disease-discordant Finnish twin pairs: one sibling suffering from Alzheimer's disease and the other being cognitively healthy. The researchers used the latest genome-wide methods to examine the twins' blood samples for any disease-related differences in epigenetic marks which are sensitive to changes in environmental factors. These differences between the siblings were discovered in multiple different genomic regions. Development of the late-onset form of Al...
Source: MDDI - Category: Medical Devices Authors: Tags: R & D Source Type: news
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 ...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Tags: Eur J Med Chem Source Type: research
Publication date: Available online 4 October 2019Source: Pharmacological ResearchAuthor(s): Amal A. Aziz, Zareen AmtulAbstractThere are many obstacles impeding the Alzheimer’s disease (AD) research. For instance, its early diagnosis to identify individuals at risk has not been successful so far. AD animal models cannot be created without genetic pre-disposition or surgical manipulation. Single gene/protein delivery has so far failed to achieve significant clinical improvements in multifactorial AD. We hypothesize that the blood-brain barrier (BBB) penetration issues are the major obstacle in the development of curren...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
We examined these clinical groups in relation to the bivariate distribution of amyloid and tau PET values. Individuals were grouped into amyloid (A)/tau (T) quadrants based on previously established abnormality cut points of s tandardized uptake value ratio 1.48 (A) and 1.33 (T). Individual participants largely fell into one of three amyloid/tau quadrants: low amyloid and low tau (A−T−), high amyloid and low tau (A+T−), or high amyloid and high tau (A+T+). Seventy per cent of cognitively unimpaired and 74% of FTD pa rticipants fell into the A−T− quadrant. Participants with mild cognitive impai...
Source: Brain - Category: Neurology Source Type: research
In conclusion, in the absence of obesity, visceral adipose tissue possesses a pronounced anti-inflammatory phenotype during aging which is further enhanced by exercise. Methods of Inducing Cellular Damage are Rarely Relevant to Aging, and the Details Matter https://www.fightaging.org/archives/2019/08/methods-of-inducing-cellular-damage-are-rarely-relevant-to-aging-and-the-details-matter/ One of the major challenges in aging research is determining whether or not models of cellular or organismal damage and its consequences are in any way relevant to the natural processes of aging. One can hit a brick with...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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