Academic literature on the topic 'Amyloidopathie'

Due to the aging population, modern society is facing an increasing prevalence of neurological diseases such as Alzheimer’s disease (AD). AD is an age-related chronic neurodegenerative disorder for which no satisfying therapy exists. Understanding the mechanisms underlying the onset of AD is necessary to find targets for protective treatment. There is growing awareness of the essential role of the immune system in the early AD pathology. Amyloidopathy, the main feature of early-stage AD, has a deregulating effect on the immune function. This is reciprocal as the immune system also affects amyloidopathy. It seems that the inflammatory reaction shows a heterogeneous pattern depending on the stage of the disease and the variation between individuals, making not only the target but also the timing of treatment important. The lack of relevant translational animal models that faithfully reproduce clinical and pathogenic features of AD is a major cause of the delay in developing new disease-modifying therapies and their optimal timing of administration. This review describes the communication between amyloidopathy and inflammation and the possibility of using nonhuman primates as a relevant animal model for preclinical AD research.

Clearance of perivascular wastes in the brain may be critical to the pathogenesis of amyloidopathies. Enlarged perivascular spaces (ePVS) on MRI have also been associated with amyloidopathies, suggesting that there may be a mechanistic link between ePVS and impaired clearance. Sleep and traumatic brain injury (TBI) both modulate clearance of amyloid-beta through glymphatic function. Therefore, we sought to evaluate the relationship between sleep, TBI, and ePVS on brain MRI. A retrospective study was performed in individuals with overnight polysomnography and 3T brain MRI consented from a single site ( n = 38). Thirteen of these individuals had a medically confirmed history of TBI. ePVS were visually assessed by blinded experimenters and analyzed in conjunction with sleep metrics and TBI status. Overall, individuals with shorter total sleep time had significantly higher ePVS burden. Furthermore, individuals with TBI showed a stronger relationship between sleep and ePVS compared to the non-TBI group. These results support the hypothesis that ePVS may be modulated by sleep and TBI, and may have implications for the role of the glymphatic system in ePVS.

A comprehensive understanding of the pathological mechanisms involved at different stages of neurodegenerative diseases is key for the advance of preventive and disease-modifying treatments. Gene expression alterations in the diseased brain is a potential source of information about biological processes affected by pathology. In this work, we performed a systematic comparison of gene expression alterations in the brains of human patients diagnosed with Alzheimer’s disease (AD) or Progressive Supranuclear Palsy (PSP) and animal models of amyloidopathy and tauopathy. Using a systems biology approach to uncover biological processes associated with gene expression alterations, we could pinpoint processes more strongly associated with tauopathy/PSP and amyloidopathy/AD. We show that gene expression alterations related to immune-inflammatory responses preponderate in younger, whereas those associated to synaptic transmission are mainly observed in older AD patients. In PSP, however, changes associated with immune-inflammatory responses and synaptic transmission overlap. These two different patterns observed in AD and PSP brains are fairly recapitulated in animal models of amyloidopathy and tauopathy, respectively. Moreover, in AD, but not PSP or animal models, gene expression alterations related to RNA splicing are highly prevalent, whereas those associated with myelination are enriched both in AD and PSP, but not in animal models. Finally, we identify 12 AD and 4 PSP genetic risk factors in cell-type specific co-expression modules, thus contributing to unveil the possible role of these genes to pathogenesis. Altogether, this work contributes to unravel the potential biological processes affected by amyloid versus tau pathology and how they could contribute to the pathogenesis of AD and PSP.

ObjectiveTo determine whether β-amyloidopathy correlates with apathy rating scores independently of mood changes and other neurodegenerative processes in Parkinson disease (PD).MethodsIn this cross-sectional study, patients with PD (n = 64, 48 male and 16 female, mean age 69.2 ± 6.7 years, Hoehn & Yahr stage 2.7 ± 0.5, Montreal Cognitive Assessment score 25.3 ± 3.0) underwent [11C]Pittsburgh compound B β-amyloid, [11C]dihydrotetrabenazine vesicular monoamine transporter type 2 (VMAT2), and [11C]methyl 4 piperidinyl propionate acetylcholinesterase brain PET imaging and clinical assessments, including the Marin Apathy Evaluation Scale, Clinician Version. Patients were recruited on the basis of having at least 1 risk factor for PD dementia, but they were excluded if they had dementia.ResultsMean apathy rating score was 25.4 ± 6.4, reflecting predominantly subclinical apathy. Apathy rating scale scores correlated with amyloid binding, cognitive, depressive, and anxiety scores but not significantly with age, duration of disease, striatal VMAT2, or cholinergic binding. Multiple regression analysis model (p < 0.0001) showed significant regressor effects for global β-amyloid burden (p = 0.0038) with significant covariate effects for global cognitive z scores (p = 0.028) and for anxiety (p = 0.038) but not with depressive scores. Voxel-based analysis showed robust correlation between apathy rating scale scores and β-amyloid binding in bilateral nuclei accumbens, inferior frontal, and cingulate cortices (family-wise error rate–corrected p < 0.005).ConclusionApathy is independently associated with β-amyloidopathy in patients with PD at risk of dementia. Regional brain findings are most robust for β-amyloidopathy in the nuclei accumbens, inferior frontal, and cingulate regions. Findings may provide an explanation for the often treatment-refractory nature of apathy in advancing PD despite optimized dopaminergic and antidepressant pharmacotherapy.ClinicalTrials.gov identifier:NCT01565473.

Amyloidopathy is one of the most prominent hallmarks of Alzheimer’s disease (AD), the leading cause of dementia worldwide, and is characterized by the accumulation of amyloid plaques in the brain parenchyma. The plaques consist of abnormal deposits mainly composed of an aggregation-prone protein fragment, [Formula: see text]-amyloid 1-40/1-42, into the extracellular matrix. Brillouin microspectroscopy is an all-optical contactless technique that is based on the interaction between visible light and longitudinal acoustic waves or phonons, giving access to the viscoelasticity of a sample on a subcellular scale. Here, we describe the first application of micromechanical mapping based on Brillouin scattering spectroscopy to probe the stiffness of individual amyloid plaques in the hippocampal part of the brain of a [Formula: see text]-amyloid overexpressing transgenic mouse. Correlative analysis based on Brillouin and Raman microspectroscopy showed that amyloid plaques have a complex structure with a rigid core of [Formula: see text]-pleated sheet conformation ([Formula: see text]-amyloid) protein surrounded by a softer ring-shaped region richer in lipids and other protein conformations. These preliminary results give a new insight into the plaque biophysics and biomechanics, and a valuable contrast mechanism for the study and diagnosis of amyloidopathy.

La prévalence des troubles neurocognitifs post-AVC (TNCPA) dans la littérature est hétérogène. Des travaux récents ont proposé une harmonisation des critères et des procédures d'évaluation cognitive post-AVC. De nombreuses études ont évalués les déterminants neuroradiologiques des TNCPA, mais peu ont évaluées le statut amyloïde. Les objectifs principaux de ce travail étaient : (1) de réaliser une méta-analyse avec revue systématique sur la prévalence et les profils des TNCPA (2) puis d'étudier la prévalence et les profils dans une cohorte française utilisant une méthodologie validée (3) d'évaluer la prévalence des dépôts amyloïdes et le devenir cognitif selon le statut amyloïde post-AVC ; (4) de préciser les corrélats neuroradiologiques du statut amyloïde et cognitif post-AVC. La population étudiée était celle de la cohorte GRECogVASC [NCT01339195] et de l'étude ancillaire IDEA 3 [NCT 02813434]. L'étude 1 montrait que plus de la moitié des patients présenterait des TNCPA, dont les deux-tiers étaient des TNC légers et un tiers des TNC majeurs. L'étude 2 démontrait que le critère optimal était le score cognitif global abrégé (c.-à-d. les performances moyennes pour la vitesse d'action, fonctions exécutives et langage). En utilisant ces critères optimisés, la prévalence des TNCPA dans la cohorte GRECogVASC était de 49,5% (IC : 44,6–54,4), dont 39% de TNC légers (IC 95% :34,4–43,9) et 10,4% de TNC majeurs (IC :7,4–13,4). L'étude 3 montrait que les dépôts amyloïdes étaient observés chez 13,5% (IC 95 : 6,39-20,58) des patients. Le statut amyloïde positif était associé à un déficit cognitif plus précoce. L'étude 4 montrait que les facteurs neuroradiologiques associés au statut amyloïde étaient : le nombre d'espaces dilatées (>10) dans les centres semi-ovales et leur présence dans la région cingulaire postérieure. Les microsaignements lobaires, l'hémosidérose et les anomalies de substance blanche temporale étaient également associées au statut amyloïde
Prevalence of post stroke neurocognitive disorders (PSNCD) is heterogeneous in the literature. Recent work has proposed the harmonization of diagnostic criteria and cognitive assessment procedures. Neuroradiological determinants of PSNCD have been studied, less other indicators as amyloid deposits. The main objectives of this work were: (1) to perform a meta-analysis with systematic review on prevalence and profiles of PSNCD; (2) to study the prevalence and profile of mild and major NCD in a French cohort, including a validated methodology (3) to assess the prevalence of post-stroke amyloid deposits and cognitive outcome according to the post-stroke amyloid status; (4) to clarify the neuroradiological correlates of amyloid and post-stroke cognitive status. The study population was the GRECogVASC cohort [NCT01339195] and the ancillary study IDEA 3 [NCT 02813434]. Study 1 showed that more than half of the patients presented with post-stroke NCD, of whom two-thirds had mild NCD and one-third had major NCD. Study 2 demonstrated that the optimal criterion was the shortened summary score (i.e., averaged performance for action speed, executive functions, and language). Using this criterion, the mean (95% confidence interval) prevalence of poststroke NCD was 49.5% (44.6–54.4), most of which corresponded to mild NCD (39.1%; 95 CI: 34.4–43.9) rather than dementia (10.4%; 95% CI:7.4–13.4). Study 3 showed that amyloid deposits were observed in 13.5% (95 CI: 6.39-20.58) of patients. A positive amyloid status was also associated with earlier cognitive impairment. Study 4 showed that neuroradiological factors associated with amyloid status were the number of dilated spaces (> 10) in the semi-oval center and their presence in the posterior cingulate region. Lobar microbleeds, hemosiderosis and temporal white matter abnormalities were also associated with the positive amyloid status