Translocator protein in late stage Alzheimer\u27s disease and Dementia with Lewy bodies brains

OBJECTIVE: Increased translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), in glial cells of the brain has been used as a neuroinflammation marker in the early and middle stages of neurodegenerative diseases, such as Alzheimer\u27s disease (AD) and Dementia with Lewy Bodies (DLB). In this study, we investigated the changes in TSPO density with respect to late stage AD and DLB. METHODS: TSPO density was measured in multiple regions of postmortem human brains in 20 different cases: seven late stage AD cases (Braak amyloid average: C; Braak tangle average: VI; Aged 74-88, mean: 83 ± 5 years), five DLB cases (Braak amyloid average: C; Braak tangle average: V; Aged 79-91, mean: 84 ± 4 years), and eight age-matched normal control cases (3 males, 5 females: aged 77-92 years; mean: 87 ± 6 years). Measurements were taken by quantitative autoradiography using [ RESULTS: No significant changes were found in TSPO density of the frontal cortex, striatum, thalamus, or red nucleus of the AD and DLB brains. A significant reduction in TSPO density was found in the substantia nigra (SN) of the AD and DLB brains compared to that of age-matched healthy controls. INTERPRETATION: This distinct pattern of TSPO density change in late stage AD and DLB cases may imply the occurrence of microglia dystrophy in late stage neurodegeneration. Furthermore, TSPO may not only be a microglia activation marker in early stage AD and DLB, but TSPO may also be used to monitor microglia dysfunction in the late stage of these diseases

SAGA: A project to automate the management of software production systems

The SAGA system is a software environment that is designed to support most of the software development activities that occur in a software lifecycle. The system can be configured to support specific software development applications using given programming languages, tools, and methodologies. Meta-tools are provided to ease configuration. The SAGA system consists of a small number of software components that are adapted by the meta-tools into specific tools for use in the software development application. The modules are design so that the meta-tools can construct an environment which is both integrated and flexible. The SAGA project is documented in several papers which are presented

Using the A/T/N framework to examine driving in preclinical Alzheimer’s disease

The A/T/N classification system is the foundation of the 2018 NIA-AA Research Framework and is intended to guide the Alzheimer disease (AD) research agenda for the next 5–10 years. Driving is a widespread functional activity that may be particularly useful in investigation of functional changes in pathological AD before onset of cognitive symptoms. We examined driving in preclinical AD using the A/T/N framework and found that the onset of driving difficulties is most associated with abnormality of both amyloid and tau pathology, rather than amyloid alone. These results have implications for participant selection into clinical trials and for the application time of interventions aimed at prolonging the time of safe driving among older adults with preclinical AD

Desde 1888 [Material gráfico proyectable]

Contiene: VI/152. Apertura del Reichstag por Guillermo II, cuadro de A. v. Werner ; VI/153. La apertura del canal de Kiel ; VI/154. Tsingtau, ciudad con la bahía ; VI/155. El monumento de Bismarck en Hamburgo ; VI/156. Bülow hablando en el Reichstag alemán, cuadro de Waltenberger ; VI/157. saludos de la flota alemana en el puerto de Kiel ; VI/158. Los Astilleros "Germania" en Kiel ; VI/159. Los establecimientos de Wertheim en Berlin ; VI/160. La estación central de Leipzig ; VI/161. El galpón para las aeronaves de Zeppelin en el lago Constantza [sic] ; VI/162. El puerto de Hamburgo ; VI/163. El vapor Vaterland saliendo del puerto de Hamburgo ; VI/164. Instalación interior de un vapor gigantesco moderno ; VI/165. La estación de Nauen ; VI/166. La torre Eiffel ; VI/167. El Banco de Inglaterra ; VI/168. El parlamento de Londres ; VI/169. El sepulcro de Cecil Rhodes ; VI/170. La ciudadela del Cairo ; VI/171. El puente sobre el Eufrates del ferrocarril de Bagdad ; VI/172. El canal de Panamá ; VI/173. Constantinopla, el Cuerno de Oro ; VI/174. El muro chino ; VI/175. Mandarines chinos ; VI/176. La insurrección de los boxers: "Los alemanes al frente", cuadro de Röchling ; VI/177. Templo japonés en Nikko ; VI/178. Mukden, vista callejera ; VI/179. El puerto de Argel ; VI/180. Tripoli, panorama de la ciudad y bahíaCopia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 2015Tit. y mención de responsabilidad tomados del catálogo de Cultura.Según DNB (Deutsche National Bibliothek), 02/07/2008, este editor estuvo activo ca. 1922-1940.El distribuidor en España de estas placas era Cultura Eimler - Basanta - Haase (Madrid)Mención de serie tomada del catálogo del distribuidor Cultura ; esta parte de la serie comienza con el n. IV/152 y termina en el IV/180

Cerebrospinal fluid neurofilament light chain is a marker of aging and white matter damage

BACKGROUND: Cerebrospinal fluid (CSF) neurofilament light chain (NfL) reflects neuro-axonal damage and is increasingly used to evaluate disease progression across neurological conditions including Alzheimer disease (AD). However, it is unknown how NfL relates to specific types of brain tissue. We sought to determine whether CSF NfL is more strongly associated with total gray matter, white matter, or white matter hyperintensity (WMH) volume, and to quantify the relative importance of brain tissue volume, age, and AD marker status (i.e., APOE genotype, brain amyloidosis, tauopathy, and cognitive status) in predicting CSF NfL. METHODS: 419 participants (Clinical Dementia Rating [CDR] Scale \u3e 0, N = 71) had CSF, magnetic resonance imaging (MRI), and neuropsychological data. A subset had amyloid positron emission tomography (PET) and tau PET. Pearson correlation analysis was used to determine the association between CSF NfL and age. Multiple regression was used to determine which brain volume (i.e., gray, white, or WMH volume) most strongly associated with CSF NfL. Stepwise regression and dominance analyses were used to determine the individual contributions and relative importance of brain volume, age, and AD marker status in predicting CSF NfL. RESULTS: CSF NfL increased with age (r = 0.59, p \u3c 0.001). Elevated CSF NfL was associated with greater total WMH volume (p \u3c 0.001), but not gray or white matter volume (p\u27s \u3e 0.05) when considered simultaneously. Age and WMH volume were consistently more important (i.e., have greater R CONCLUSIONS: CSF NfL is a non-specific marker of aging and white matter integrity with limited sensitivity to specific markers of AD. CSF NfL likely reflects processes associated with cerebrovascular disease

Brain age predicts disability accumulation in multiple sclerosis

OBJECTIVE: Neurodegenerative conditions often manifest radiologically with the appearance of premature aging. Multiple sclerosis (MS) biomarkers related to lesion burden are well developed, but measures of neurodegeneration are less well-developed. The appearance of premature aging quantified by machine learning applied to structural MRI assesses neurodegenerative pathology. We assess the explanatory and predictive power of brain age analysis on disability in MS using a large, real-world dataset. METHODS: Brain age analysis is predicated on the over-estimation of predicted brain age in patients with more advanced pathology. We compared the performance of three brain age algorithms in a large, longitudinal dataset (\u3e13,000 imaging sessions from \u3e6,000 individual MS patients). Effects of MS, MS disease course, disability, lesion burden, and DMT efficacy were assessed using linear mixed effects models. RESULTS: MS was associated with advanced predicted brain age cross-sectionally and accelerated brain aging longitudinally in all techniques. While MS disease course (relapsing vs. progressive) did contribute to advanced brain age, disability was the primary correlate of advanced brain age. We found that advanced brain age at study enrollment predicted more disability accumulation longitudinally. Lastly, a more youthful appearing brain (predicted brain age less than actual age) was associated with decreased disability. INTERPRETATION: Brain age is a technically tractable and clinically relevant biomarker of disease pathology that correlates with and predicts increasing disability in MS. Advanced brain age predicts future disability accumulation

Quantitative signal properties from standardized MRIs correlate with multiple sclerosis disability

OBJECTIVE: To enable use of clinical magnetic resonance images (MRIs) to quantify abnormalities in normal appearing (NA) white matter (WM) and gray matter (GM) in multiple sclerosis (MS) and to determine associations with MS-related disability. Identification of these abnormalities heretofore has required specialized scans not routinely available in clinical practice. METHODS: We developed an analytic technique which normalizes image intensities based on an intensity atlas for quantification of WM and GM abnormalities in standardized MRIs obtained with clinical sequences. Gaussian mixture modeling is applied to summarize image intensity distributions from T1-weighted and 3D-FLAIR (T2-weighted) images from 5010 participants enrolled in a multinational database of MS patients which collected imaging, neuroperformance and disability measures. RESULTS: Intensity distribution metrics distinguished MS patients from control participants based on normalized non-lesional signal differences. This analysis revealed non-lesional differences between relapsing MS versus progressive MS subtypes. Further, the correlation between our non-lesional measures and disability was approximately three times greater than that between total lesion volume and disability, measured using the patient derived disease steps. Multivariate modeling revealed that measures of extra-lesional tissue integrity and atrophy contribute uniquely, and approximately equally, to the prediction of MS-related disability. INTERPRETATION: These results support the notion that non-lesional abnormalities correlate more strongly with MS-related disability than lesion burden and provide new insight into the basis of abnormalities in NA WM. Non-lesional abnormalities distinguish relapsing from progressive MS but do not distinguish between progressive subtypes suggesting a common progressive pathophysiology. Image intensity parameters and existing biomarkers each independently correlate with MS-related disability