Circulating Interleukin-6 Levels and Incident Ischemic Stroke: A Systematic Review and Meta-analysis of Prospective Studies.

Background And Objectives: Human genetic studies support a key role of interleukin-6 (IL-6) in the pathogenesis of ischemic stroke. However, there are only limited data from observational studies exploring circulating IL-6 levels as a risk factor for ischemic stroke. We set out to perform a systematic review and meta-analysis of aggregate data on cohort studies to determine the magnitude and shape of the association between circulating IL-6 levels and risk of incident ischemic stroke in the general population.

Diabetes Mellitus, Glycemic Traits, and Cerebrovascular Disease: A Mendelian Randomization Study.

Objective: We employed Mendelian randomization to explore the effects of genetic predisposition to type 2 diabetes (T2D), hyperglycemia, insulin resistance, and pancreatic β-cell dysfunction on risk of stroke subtypes and related cerebrovascular phenotypes.

Methods: We selected instruments for genetic predisposition to T2D (74,124 cases, 824,006 controls), HbA1c levels (n = 421,923), fasting glucose levels (n = 133,010), insulin resistance (n = 108,557), and β-cell dysfunction (n = 16,378) based on published genome-wide association studies. Applying 2-sample Mendelian randomization, we examined associations with ischemic stroke (60,341 cases, 454,450 controls), intracerebral hemorrhage (1,545 cases, 1,481 controls), and ischemic stroke subtypes (large artery, cardioembolic, small vessel stroke), as well as with related phenotypes (carotid atherosclerosis, imaging markers of cerebral white matter integrity, and brain atrophy).

Cerebrospinal Fluid Levels of Kininogen-1 Indicate Early Cognitive Impairment in Parkinson's Disease.

Background: Cognitive impairment is common in patients with PD. Core markers of Alzheimer's dementia have been related also to PD dementia, but no disease-specific signature to predict PD dementia exists to date.

Objectives: The aim of this study was to investigate CSF markers associated with cognition in early PD.

Genetically determined blood pressure, antihypertensive drug classes, and risk of stroke subtypes.

Objective: We employed Mendelian randomization to explore whether the effects of blood pressure (BP) and BP-lowering through different antihypertensive drug classes on stroke risk vary by stroke etiology.

Methods: We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drug targets from genome-wide association studies (GWAS) on 757,601 individuals. Applying 2-sample Mendelian randomization, we examined associations with any stroke (67,162 cases; 454,450 controls), ischemic stroke and its subtypes (large artery, cardioembolic, small vessel stroke), intracerebral hemorrhage (ICH, deep and lobar), and the related small vessel disease phenotype of white matter hyperintensities (WMH).

MERLIN: a novel BRET-based proximity biosensor for studying mitochondria-ER contact sites.

The contacts between the ER and mitochondria play a key role in cellular functions such as the exchange of lipids and calcium between both organelles, as well as in apoptosis and autophagy signaling. The molecular architecture and spatiotemporal regulation of these distinct contact regions remain obscure and there is a need for new tools that enable tackling these questions. Here, we present a new bioluminescence resonance energy transfer-based biosensor for the quantitative analysis of distances between the ER and mitochondria that we call MERLIN (Mitochondria-ER Length Indicator Nanosensor).

Monoamine oxidase-A promotes protective autophagy in human SH-SY5Y neuroblastoma cells through Bcl-2 phosphorylation.

Monoamine oxidases (MAOs) are located on the outer mitochondrial membrane and are drug targets for the treatment of neurological disorders. MAOs control the levels of neurotransmitters in the brain via oxidative deamination and contribute to reactive oxygen species (ROS) generation through their catalytic by-product HO. Increased ROS levels may modulate mitochondrial function and mitochondrial dysfunction is implicated in a vast array of disorders.

Cost of diagnosing dementia in a German memory clinic.

Background: Little is known about diagnostic work-ups or the costs of diagnosing dementia in specialized care. Here, we analyzed the costs of diagnosing dementia according to specific dementia disorders.

Methods: A prospective descriptive design was used to analyze the cost of diagnosing dementia for 120 patients with suspected dementia at a German memory clinic.

Neuroimaging Biomarkers Predict Brain Structural Connectivity Change in a Mouse Model of Vascular Cognitive Impairment.

Background And Purpose: Chronic hypoperfusion in the mouse brain has been suggested to mimic aspects of vascular cognitive impairment, such as white matter damage. Although this model has attracted attention, our group has struggled to generate a reliable cognitive and pathological phenotype. This study aimed to identify neuroimaging biomarkers of brain pathology in aged, more severely hypoperfused mice.

Novel cases of amyotrophic lateral sclerosis after treatment of cerebral arteriovenous malformationss.

Previous case studies reported nine patients with cerebral arteriovenous malformations (AVM) who developed amyotrophic lateral sclerosis (ALS) after AVM embolisation. Here, we describe three novel cases of ALS which developed 13-34 years after treatment, including embolisation, of cerebral AVM. This study provides further arguments supporting the thesis that embolisation of cerebral AVM might influence the risk of later ALS development.

Parkinson's disease: From human genetics to clinical trials.

Combining genetic insights into the pathogenesis of Parkinson's disease (PD) with findings from animal and cellular models of this disorder has advanced our understanding of the pathways that lead to the characteristic degeneration of dopaminergic neurons in the brain's nigrostriatal pathway. This has fueled an increase in candidate compounds designed to modulate these pathways and to alter the processes underlying neuronal death in this disorder. Using mitochondrial quality control and the macroautophagy/lysosomal pathways as examples, we discuss the pipeline from a comprehensive genetic architecture for PD through to clinical trials for drugs targeting pathways linked to neurodegeneration in PD.

Logopenic, mixed, or Alzheimer-related aphasia?

Objective: This study tested the hypothesis that patients with primary progressive aphasia (PPA) who do not meet the proposed criteria for any of the recognized subtypes would have the atrophy pattern reported in the past for logopenic variant PPA (lvPPA), in turn suggesting that the PPA of likely Alzheimer disease origin is more variable than that captured in the current lvPPA diagnostic recommendations.

Methods: MRI gray matter volumes from 14 patients with mixed PPA who failed to meet the diagnostic recommendations for any recognized variant were compared with those of 25 matched control participants via voxel-based morphometry.

Results: The mixed PPA group had left temporoparietal atrophy with a pattern identical to that in previously reported lvPPA cohorts.

Differentiation between idiopathic and atypical parkinsonian syndromes using three-dimensional magnetic resonance spectroscopic imaging.

Objectives: Degeneration of dopaminergic neurons in the substantia nigra (SN) pars compacta is the primary cause of idiopathic Parkinson's disease (iPD). In early stages of disease in particular, presentation of symptoms is non-specific leading to difficulties in differentiating between iPD and atypical parkinsonian syndromes (aPS). The aim of this study was to evaluate the feasibility of three-dimensional magnetic resonance spectroscopic imaging (MRSI) of the SN region for differentiation between iPD and aPS.