Lycopene mitigates β-amyloid induced inflammatory response and inhibits NF-κB signaling at the choroid plexus in early stages of Alzheimer’s disease rats

2018 ◽  
Vol 53 ◽  
pp. 66-71 ◽  
Author(s):  
Chong-Bin Liu ◽  
Rui Wang ◽  
Yan-Feng Yi ◽  
Zhen Gao ◽  
Yi-Zhu Chen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Response ◽  
Choroid Plexus ◽  
Early Stages ◽  
Β Amyloid

scholarly journals Intracerebral Injection of Extracellular Vesicles from Mesenchymal Stem Cells Exerts Reduced Aβ Plaque Burden in Early Stages of a Preclinical Model of Alzheimer’s Disease

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1059 ◽  
Author(s):  
Chiara A. Elia ◽  
Matteo Tamborini ◽  
Marco Rasile ◽  
Genni Desiato ◽  
Sara Marchetti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Clinical Manifestations ◽  
Plaque Burden ◽  
Intracerebral Injection ◽  
Early Stages ◽  
Β Amyloid

Bone marrow Mesenchymal Stem Cells (BM-MSCs), due to their strong protective and anti-inflammatory abilities, have been widely investigated in the context of several diseases for their possible therapeutic role, based on the release of a highly proactive secretome composed of soluble factors and Extracellular Vesicles (EVs). BM-MSC-EVs, in particular, convey many of the beneficial features of parental cells, including direct and indirect β-amyloid degrading-activities, immunoregulatory and neurotrophic abilities. Therefore, EVs represent an extremely attractive tool for therapeutic purposes in neurodegenerative diseases, including Alzheimer’s disease (AD). We examined the therapeutic potential of BM-MSC-EVs injected intracerebrally into the neocortex of APPswe/PS1dE9 AD mice at 3 and 5 months of age, a time window in which the cognitive behavioral phenotype is not yet detectable or has just started to appear. We demonstrate that BM-MSC-EVs are effective at reducing the Aβ plaque burden and the amount of dystrophic neurites in both the cortex and hippocampus. The presence of Neprilysin on BM-MSC-EVs, opens the possibility of a direct β-amyloid degrading action. Our results indicate a potential role for BM-MSC-EVs already in the early stages of AD, suggesting the possibility of intervening before overt clinical manifestations.

Neurogenic effects of β-amyloid in the choroid plexus epithelial cells in Alzheimer’s disease

2013 ◽  
Vol 70 (15) ◽  
pp. 2787-2797 ◽  
Author(s):  
Marta Bolos ◽  
Carlos Spuch ◽  
Lara Ordoñez-Gutierrez ◽  
Francisco Wandosell ◽  
Isidro Ferrer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Epithelial Cells ◽  
Choroid Plexus ◽  
Β Amyloid ◽  
Choroid Plexus Epithelial

scholarly journals Modulation of glucose metabolism and metabolic connectivity by β-amyloid

2016 ◽  
Vol 36 (12) ◽  
pp. 2058-2071 ◽  
Author(s):  
Felix Carbonell ◽  
Alex P Zijdenbos ◽  
Donald G McLaren ◽  
Yasser Iturria-Medina ◽  
Barry J Bedell ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Metabolism ◽  
Disease Process ◽  
Continuous Variable ◽  
Amyloid Burden ◽  
Early Stages ◽  
Metabolic Connectivity ◽  
Β Amyloid ◽  
Glucose Hypometabolism

Glucose hypometabolism in the pre-clinical stage of Alzheimer’s disease (AD) has been primarily associated with the APOE ɛ4 genotype, rather than fibrillar β-amyloid. In contrast, aberrant patterns of metabolic connectivity are more strongly related to β-amyloid burden than APOE ɛ4 status. A major limitation of previous studies has been the dichotomous classification of subjects as amyloid-positive or amyloid-negative. Dichotomous treatment of a continuous variable, such as β-amyloid, potentially obscures the true relationship with metabolism and reduces the power to detect significant changes in connectivity. In the present work, we assessed alterations of glucose metabolism and metabolic connectivity as continuous function of β-amyloid burden using positron emission tomography scans from the Alzheimer’s Disease Neuroimaging Initiative study. Modeling β-amyloid as a continuous variable resulted in better model fits and improved power compared to the dichotomous model. Using this continuous model, we found that both APOE ɛ4 genotype and β-amyloid burden are strongly associated with glucose hypometabolism at early stages of Alzheimer’s disease. We also determined that the cumulative effects of β-amyloid deposition result in a particular pattern of altered metabolic connectivity, which is characterized by global, synchronized hypometabolism at early stages of the disease process, followed by regionally heterogeneous, progressive hypometabolism.

scholarly journals Failure of the choroid plexus in Alzheimer's disease

2021 ◽  
Author(s):  
Maria Carna ◽  
Isaac G Onyango ◽  
Stanislav Katina ◽  
Dusan Holub ◽  
Marketa Nezvezdova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Inflammatory Response ◽  
Cognitive Decline ◽  
Choroid Plexus ◽  
Neurodegenerative Disorder ◽  
Protein Accumulation ◽  
Amyloid Peptides ◽  
Inflammatory Changes

Alzheimer's disease is a neurodegenerative disorder characterized clinically by cognitive decline and pathologically by amyloid deposition and neurofibrillary changes. These neuropathological hallmarks are accompanied by reactive events including microglial activation and astrogliosis. The inflammatory response in Alzheimer's disease brains is distinguished by a pro-inflammatory signature involving amyloid peptides, inflammasome signalling and disrupted blood brain barrier. Inflammatory changes are observed also in the cerebrospinal fluid in Alzheimer's disease. It remains unknown, however, whether the choroid plexus which produces cerebrospinal fluid and guards the brain from peripheral inflammatory insults, contributes to the inflammation and pathogenesis of Alzheimer's disease. Here we show that the choroid plexus in Alzheimer's disease exhibits a pro-inflammaotory signature with aberrant protein accumulation, which contribute to the age-dependent inflammatory changes observed in the cerebrospinal fluid. Magnetic resonance imaging reveals that the choroid plexus in patients with Alzheimer's disease displays pathological signal and increased volume, which inversely correlates with cognitive decline. Our findings suggest that the choroid plexus, being unable to efficiently resolve inflammatory insults over the lifetime, eventually ignites and drives the aberrant inflammatory response observed in Alzheimer's disease. These findings advance our understanding of the pathogenesis and open new vistas in the diagnostics and therapeutics of Alzheimer's disease.

P2-013: ANNEXIN V INHIBITS β-AMYLOID-INDUCED CITOTOXITY IN CHOROID PLEXUS: IMPLICATIONS FOR ALZHEIMER'S DISEASE

2014 ◽  
Vol 10 ◽  
pp. P475-P475
Author(s):  
Agnieszka Krzyzanowska ◽  
Eva Carro ◽  
Fernando Bartolome ◽  
Ines Garcia-Consuegra ◽  
Consuelo Pascual ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Choroid Plexus ◽  
Annexin V ◽  
Β Amyloid

scholarly journals Predicting future regional tau accumulation in asymptomatic and early Alzheimer’s disease

2020 ◽  
Author(s):  
Joseph Giorgio ◽  
William Jagust ◽  
Suzanne Baker ◽  
Susan Landau ◽  
Peter Tino ◽  
...  
Keyword(s):  
Machine Learning ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Trial Design ◽  
Clinical Trial Design ◽  
Learning Approach ◽  
Early Stages ◽  
Machine Learning Approach ◽  
Β Amyloid

Abstract The earliest stages of Alzheimer’s disease (AD) involve interactions between multiple pathophysiological processes. Although these processes are well studied, we still lack robust tools to predict individualised trajectories of disease progression. Here, we employ a robust and interpretable machine learning approach to combine multimodal biological data and predict future tau accumulation, translating predictive information from deep phenotyping cohorts at early stages of AD to cognitively normal individuals. In particular, we use machine learning to quantify interactions between key pathological markers (β-amyloid, medial temporal atrophy, tau and APOE 4) at early and asymptomatic stages of AD. We next derive a predictive index that stratifies individuals based on future pathological tau accumulation, highlighting two critical features for optimal clinical trial design. First, future tau accumulation provides a better outcome measure compared to changes in cognition. Second, stratification based on multimodal data compared to β-amyloid alone reduces the sample size required to detect a clinically meaningful change in tau accumulation. Further, we extend our machine learning approach to derive individualised trajectories of future pathological tau accumulation in early AD patients and accurately predict regional future rate of tau accumulation in an independent sample of cognitively unimpaired individuals. Our results propose a robust approach for fine scale stratification and prognostication with translation impact for clinical trial design at asymptomatic and early stages of AD.

Sign in / Sign up

Export Citation Format

Share Document