Journal Article

The C9orf72 hexanucleotide repeat expansion mutation is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, but its cell type-specific effects on energy metabolism and immune pathways remain poorly understood. Using induced pluripotent stem cell (iPSC)-derived motor neurons, astrocytes, and microglia from C9orf72 patients and their isogenic controls, we investigated metabolic changes at the single-cell level under basal and inflammatory conditions. [...]

Eukaryotic cells rely on mitochondria to fine-tune their metabolism in response to environmental and nutritional changes. However, how mitochondria adapt to nutrient availability and how diets impact mitochondrial disease progression, remain unclear. [...]

Cell-free microRNAs in body fluids have emerged as promising biomarker candidates in neurodegenerative diseases. While several studies have identified dysregulated miRNAs in sporadic Parkinson's disease, it remains unclear whether distinguishable alterations of cell-free miRNAs occur in genetic forms of the disease, such as those associated with the LRRK2 G2019S mutation. [...]

Sporadic late-onset cerebellar ataxia (SLOCA) is a syndrome defined by subacute or chronic and progressive ataxia occurring after the age of 40 years in individuals without a family history of ataxia. The 2022 publication of revised consensus diagnostic criteria for multiple system atrophy and the emergence of promising biomarkers provides a thorough diagnostic framework that now enables the diagnosis of numerous acquired causes of SLOCA, including autoimmune disorders and neurodegenerative diseases. [...]

Analysis of the frequency of comorbid Alzheimer's disease in patients with suspected idiopathic normal pressure hydrocephalus (iNPH) and its effects on the response to cerebrospinal fluid (CSF) drainage as well as analysis of the frequency of a vascular copathology in patients with suspected iNPH.This was a prospective observational analysis of patients with suspected iNPH who underwent guideline-conform NPH routine diagnostics including CSF drainage during clinical routine diagnostics between 1 July 2022 and 30 June 2023. Patients were recruited via the departments of neurology, neurosurgery and psychiatry of the University Hospital Carl Gustav Carus in Dresden. [...]

Since the advent of optogenetics, great progress has been made in developing tools to modulate and detect cellular activity using light. We present a two-component optogenetic silencing tool, RoCK (rhodopsin cyclase/K+ channel), which pairs the rhodopsin-guanylyl cyclase CaRhGC with customized SthK K+ channels that are engineered to open selectively upon guanosine 3',5'-monophosphate (cGMP) binding. [...]

Clinical progression rate is the typical primary endpoint measure in progressive supranuclear palsy (PSP) clinical trials.This longitudinal multicohort study investigated whether baseline clinical severity and regional brain atrophy could predict clinical progression in PSP-Richardson's syndrome (PSP-RS).PSP-RS patients (n = 309) from the placebo arms of clinical trials (NCT03068468, NCT01110720, NCT02985879, NCT01049399) and DescribePSP cohort were included. We investigated associations of baseline clinical and volumetric magnetic resonance imaging (MRI) data with 1-year longitudinal PSP rating scale (PSPRS) change. [...]

The International Statistical Classification of Diseases and Related Health Problems version 11 (ICD-11) represents a conceptual advance over ICD-10 in the classification of dementias. Although the syndromic classification in the chapter 'Neurocognitive disorders' remains in principle unchanged, the introduction of severity levels and the central positioning of mental and behavioral symptoms enables a more precise coding of the clinical diagnoses. [...]

BackgroundThe association between lifestyle factors and Alzheimer's disease (AD) pathophysiology remains incompletely understood.ObjectiveThe aim of this study was to assess the association of alcohol consumption, smoking behavior, sleep quality and physical, cognitive, and social activity with cerebral amyloid pathology.MethodsFor this cross-sectional study, we selected participants from the Amyloid Biomarker Study data pooling initiative. We used generalized estimating equations to assess associations of dichotomized lifestyle measures with amyloid pathology.ResultsWe included 9171 participants with normal cognition (NC) and 2555 participants with mild cognitive impairment (MCI) from the Amyloid Biomarker Study. [...]