Search results for "amyloidosis"

Crosstalk between angiotensin and the nonamyloidogenic pathway of Alzheimer's amyloid precursor protein.

2017

The association between hypertension and an increased risk for Alzheimer's disease (AD) and dementia is well established. Many data suggest that modulation of the renin-angiotensin system may be meaningful for the prevention and therapy of neurodegenerative disorders, in particular AD. Proteolytic cleavage of the amyloid precursor protein (APP) by α-secretase precludes formation of neurotoxic Aβ peptides and is expected to counteract the development of AD. An established approach for the up-regulation of α-secretase cleavage is the activation of G protein-coupled receptors (GPCRs). Therefore, our study aimed to analyze whether stimulation of angiotensin AT1 or AT2 receptors stably expressed…

FMF is not always "fever": from clinical presentation to "treat to target".

2020

AbstractFamilial Mediterranean Fever, a monogenic autoinflammatory disease secondary to MEFV gene mutations in the chromosome 16p13, is characterized by recurrent self-limiting attacks of fever, arthritis, aphthous changes in lips and/or oral mucosa, erythema, serositis. It is caused by dysregulation of the inflammasome, a complex intracellular multiprotein structure, commanding the overproduction of interleukin 1. Familial Mediterranean Fever can be associated with other multifactorial autoinflammatory diseases, as vasculitis and Behçet disease.Symptoms frequently start before 20 years of age and are characterized by a more severe phenotype in patients who begin earlier.Attacks consist of …

Expression of endogenous mouse APP modulates β-amyloid deposition in hAPP-transgenic mice

2017

Amyloid-β (Aβ) deposition is one of the hallmarks of the amyloid hypothesis in Alzheimer’s disease (AD). Mouse models using APP-transgene overexpression to generate amyloid plaques have shown to model only certain parts of the disease. The extent to which the data from mice can be transferred to man remains controversial. Several studies have shown convincing treatment results in reducing Aβ and enhancing cognition in mice but failed totally in human. One model-dependent factor has so far been almost completely neglected: the endogenous expression of mouse APP and its effects on the transgenic models and the readout for therapeutic approaches. Here, we report that hAPP-transgenic models of …

Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?

2018

The cascade of molecular events leading to Human apolipoprotein A–I (apoA–I) amyloidosis is not completely understood, not even the pathways that determine clinical manifestations associated to systemic protein deposition in organs such as liver, kidney and heart. About twenty natural variants of apoA–I were described as inducing amyloidosis, but the mechanisms driving their aggregation and deposition are still unclear. We previously identified that the mutant Gly26Arg but not Lys107-0 induced the release of cytokines and reactive oxygen species from cultured RAW 264.7 murine macrophages, suggesting that part of the pathogenic pathway could elicit of an inflammatory signal. In this work we …

Transthyretin familial amyloid polyneuropathy (TTR‐FAP): Parameters for early diagnosis

2017

Abstract Background Familial transthyretin amyloidosis is a life‐threatening disease presenting with sensorimotor and autonomic polyneuropathy. Delayed diagnosis has a detrimental effect on treatment and prognosis. To facilitate diagnosis, we analyzed data patterns of patients with transthyretin familial amyloid polyneuropathy (TTR‐FAP) and compared them to polyneuropathies of different etiology for clinical and electrophysiological discriminators. Methods Twenty‐four patients with TTR‐FAP and 48 patients with diabetic polyneuropathy (dPNP) were investigated (neurological impairment score NIS; neurological disability score NDS) in a cross‐sectional design. Both groups were matched for gende…

Short-Term Effects of Microglia-Specific Mitochondrial Dysfunction on Amyloidosis in Transgenic Models of Alzheimer's Disease.

2018

Reduction of mitochondrial activity is a subtle and early event in the pathogenesis of Alzheimer’s disease. Mitochondrial damage and consequentially enhanced production of reactive oxygen species is particularly occurring in the vicinity of amyloid plaques. Since all cells are affected by mitochondrial damage, analyses of cell type-specific effects are challenging. To study the impact of mitochondrial alterations on microglial activity in a homogeneous genetic background, we generated bone marrow chimeras of irradiated 46-days-old APP-transgenic mice. For reconstitution, bone marrow from CX3CR1-eGFP mice with mitochondria of either non-obese diabetic or C57BL/6J animals was utilized. Succes…

2020

The term “amyloid” refers to proteinaceous deposits of peptides that might be generated from larger precursor proteins e.g., by proteolysis. Common to these peptides is a stable cross-β dominated secondary structure which allows self-assembly, leading to insoluble oligomers and lastly to fibrils. These highly ordered protein aggregates have been, for a long time, mainly associated with human neurodegenerative diseases such as Alzheimer’s disease (Amyloid-β peptides). However, they also exert physiological functions such as in release of deposited hormones in human beings. In the light of the rediscovery of our microbial commensals as important companions in health and disease, the fact that…

Cardiac MR enables diagnosis in 90% of patients with acute chest pain, elevated biomarkers and unobstructed coronary arteries

2015

To assess the diagnostic value of cardiac MRI (CMR) in patients with acute chest pain, elevated cardiac enzymes and a negative coronary angiogram.This study included a total of 125 patients treated in the chest pain unit during a 39-month period. Each included patient underwent MRI within a median of 3 days after cardiac catheterization. The MRI protocol comprised cine, oedema-sensitive and late gadolinium-enhancement imaging. The standard of reference was a consensus diagnosis based on clinical follow-up and the synopsis of all clinical, laboratory and imaging data.MRI revealed a multitude of diagnoses, including ischaemic cardiomyopathy (CM), dilated CM, myocarditis, Takotsubo CM, hyperte…

Manifestation and ultrastructural typing of amyloid deposits in the heart

1983

Using light and electron microscopy, 65 cases of amyloid deposits in the heart were examined. Five different groups were distinguished: I. isolated atrial amyloidosis, II. senile cardiac amyloidosis, III. cardiac amyloid accompanying chronic infections and tumors, IV. cardiac amyloid accompanying plasma cell dyscrasia, V. idiopathic cardiac amyloidosis. Seen structurally, no principal differences in the precise localization of the amyloid deposits were found in any of the groups investigated. Amyloid is always deposited in the vicinity of cells with myocytic cell differentiation (i.e. the heart muscle cells, non-striated muscle cells of the vessels), whereby the relevant basement membranes …

Alzheimer's disease: amyloid plaques in the cerebellum

1989

Two specific silver-staining methods demonstrating either extracellular amyloid and/or precursors of amyloid or intraneuronal neurofibrillary changes were used to examine cerebellar pathology in cases of presenile and senile dementia of the Alzheimer type, cases of Down's syndrome, and non-demented controls. The sensitivity of the techniques permitted visualization of large numbers of amyloid deposits in the cerebellar cortex of demented individuals. Similarly large numbers of amyloid deposits were not found in the cerebella of non-demented individuals. Neurofibrillary changes were absent. The majority of amyloid plaques occurred in the molecular layer. Quite a number of these displayed lar…