Oligomeric Forms of Human Amyloid-Beta(1 –42) Inhibit Antigen Presentation

Genetic, clinical, biochemical and histochemical data indicate a crucial involvement of inflammation in Alzheimer's disease (AD), but harnessing the immune system to cure or prevent AD has so far proven difficult. Clarifying the cellular heterogeneity and signaling pathways associated with the presence of the AD hallmarks beta-amyloid and tau in the brain, would help to identify potential targets for therapy. While much attention has been so far devoted to microglia and their homeostatic phagocytic activity, additional cell types and immune functions might be affected in AD. Beyond microglia localized in the brain parenchyma, additional antigen-presenting cell (APC) types might be affected by beta-amyloid toxicity. Here, we investigated potential immunomodulatory properties of oligomeric species of beta-amyloid-peptide (Aβ) on microglia and putative APCs. We performed a comprehensive characterization of time- and pathology-dependent APC and T-cell alterations in a model of AD-like brain beta-amyloidosis, the APP-PS1-dE9 mouse model. We show that the deposition of first beta-amyloid plaques is accompanied by a significant reduction in MHC class II surface levels on brain APCs. Furthermore, taking advantage of customized in vitro systems and RNAseq, we demonstrate that a preparation containing various forms of oligomeric Aβ1-42 inhibits antigen presentation by altering the transcription of key immune mediators in dendritic cells. These results suggest that, beyond the...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Intra-gastrointestinal amyloid-β1-42 oligomers perturb enteric function and induce Alzheimer's disease pathology. J Physiol. 2020 Jul 02;: Authors: Sun Y, Sommerville NR, Liu JYH, Ngan MP, Poon D, Ponomarev ED, Lu Z, Kung JSC, Rudd JA Abstract KEY POINTS: Alzheimer's disease (AD) patients and transgenic mice have beta-amyloid (Aβ) aggregation in the gastrointestinal (GI) tract. It is possible that Aβ from the periphery contributes to the load of Aβ in the brain, as Aβ has prion-like properties. The present investigations demonstrate that Aβ injected into the GI tract of I...
Source: The Journal of Physiology - Category: Physiology Authors: Tags: J Physiol Source Type: research
Conclusion: 11C-metoclopramide can measure ABCB1 induction in the mouse brain without the need to consider an arterial input function and may find potential application in Alzheimer disease patients to noninvasively evaluate strategies to enhance the clearance properties of the BBB.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Basic Source Type: research
This genetic association study examines amyloid levels through positron emission tomographic imaging in individuals with or at risk for Alzheimer disease.
Source: JAMA Neurology - Category: Neurology Source Type: research
af GM Abstract Alzheimer's disease (AD) is a progressive brain amyloidosis that damages brain regions associated with memory, thinking, behavioral and social skills. Neuropathologically AD is characterized by intraneuronal hyperphosphorylated tau inclusions as neurofibrillary tangles (NFTs), and buildup of extracellular amyloid beta (Aβ) peptide as senile plaques. Several biomarker tests capturing these pathologies have been developed. However, for the full clinical expression of the neurodegenerative events of AD, there are presence of other central molecular pathways. In terms of understanding the unidentif...
Source: Current Topics in Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Top Med Chem Source Type: research
We report here, in simian immunodeficiency virus (SIV)+ rhesus macaques and patients diagnosed with HIV, brain region–specific up-regulation of amyloid precursor protein (APP) and Aβ (40 and 42) in astrocytes. In addition, we find increased expression of β-site cleaving enzyme (BACE1), APP, and Aβ in human primary astrocytes (HPAs) exposed to Tat. Mechanisms involved up-regulation of hypoxia- inducible factor (HIF-1α), its translocation and binding to the long noncoding RNA (lncRNA) BACE1‐antisense transcript (BACE1-AS), resulting, in turn, in the formation of the BACE1-AS/BACE1 RNA complex, su...
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research
We reported similar impairments in 3xTg-AD mice learning a spatial reorientation task. Memory reactivation during sleep is critical for learning-related plasticity, and memory consolidation is correlated with hippocampal sharp wave ripple (SWR) density, cortical delta waves (DWs), cortical spindles, and the temporal coupling of these events-postulated as physiological substrates for memory consolidation. Further, hippocampal-cortical discoordination is prevalent in individuals with AD. Thus, we hypothesized that impaired memory consolidation mechanisms in hippocampal-cortical networks could account for spatial memory defic...
Source: Current Biology - Category: Biology Authors: Tags: Curr Biol Source Type: research
We report that CCL2 overexpression aggravated tau pathology in rTg4510 as shown by the increase in Gallyas stained neurofibrillary tangles as well as phosphorylated tau-positive inclusions. In addition, biochemical analysis showed a reduction in the levels of detergent-soluble tau species followed by increase in the insoluble fraction, indicating a shift toward larger tau aggregates. Indeed, increased levels of high molecular weight species of phosphorylated tau were found in the mice injected with CCL2. We also report that worsening of tau pathology following CCL2 overexpression was accompanied by a distinct inflammatory ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
284Background: Understanding the time course of amyloid-beta (Aβ) aggregation in Alzheimer’s disease (AD) is important for understanding the chronological sequence of events in the AD continuum. This work uses serial [11C]Pittsburgh Compound B (PiB) PET imaging data to 1) characterize the relationship between rates of Aβ accumulation and Aβ burden, and 2) estimate the time course of PiB-measure Aβ accumulation by applying a novel algorithm that uses a combination of Euler’s method with discrete sampling. Methods: 181 initially cognitively unimpaired participants from the Wisconsin Registry f...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Amyloid & amp; Tau PET Source Type: research
This article will explore the etiology, those most commonly affected, types, appearance, treatment, prognosis, etc. Research began by focusing on amyloidosis in general then diving in further looking specifically at cardiac amyloid and PET amyloid imaging. Each article describes amyloidosis as a very rare disease that affects predominantly a male population between the ages of 30 and 80. There are several different types of amyloidosis that affect an array of organs including the heart, nerves, digestive system, and the kidneys. Nuclear Medicine, using small amounts of radiation, can help diagnose cardiac amyloidosis and a...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Tech Students (Poster Session) Source Type: research
Conclusions: A method has been developed that uses freely available software to co-register a mouse brain atlas to a cohort of micro PET-CT images, enabling uptake assessment of cerebral VOIs with minimal computational demand. References: 1Janke AL, Ullmann JF. (2015) Robust methods to create ex vivo minimum deformation atlases for brain mapping. Methods. 2015 Feb;73:18-26. doi: 10.1016/j.ymeth.2015.01.005 2M. Jenkinson, C.F. Beckmann, T.E. Behrens, M.W. Woolrich, S.M. Smith. FSL. NeuroImage, 62:782-90, 2012 Figure 1: (Top row) A skull-cropped CT image in the Sagittal and Transaxial planes with the skull cavity mask shown ...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Basic Science - New tracers/analysis Source Type: research
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