Bringing CLARITY to the human brain: visualization of Lewy pathology in three dimensions.

Neuropathol Appl Neurobiol

Neuropathology Unit, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.

Published: October 2016

Aims: CLARITY is a novel technique which enables three-dimensional visualization of immunostained tissue for the study of circuitry and spatial interactions between cells and molecules in the brain. In this study, we aimed to compare methodological differences in the application of CLARITY between rodent and large human post mortem brain samples. In addition, we aimed to investigate if this technique could be used to visualize Lewy pathology in a post mortem Parkinson's brain.

Methods: Rodent and human brain samples were clarified and immunostained using the passive version of the CLARITY technique. Samples were then immersed in different refractive index matching media before mounting and visualizing under a confocal microscope.

Results: We found that tissue clearing speed using passive CLARITY differs according to species (human vs. rodents), brain region and degree of fixation (fresh vs. formalin-fixed tissues). Furthermore, there were advantages to using specific refractive index matching media. We have applied this technique and have successfully visualized Lewy body inclusions in three dimensions within the nucleus basalis of Meynert, and the spatial relationship between monoaminergic fibres and Lewy pathologies among nigrostriatal fibres in the midbrain without the need for physical serial sectioning of brain tissue.

Conclusions: The effective use of CLARITY on large samples of human tissue opens up many potential avenues for detailed pathological and morphological studies.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053282PMC
http://dx.doi.org/10.1111/nan.12293DOI Listing

Publication Analysis

Top Keywords

human brain
8
lewy pathology
8
three dimensions
8
post mortem
8
brain samples
8
refractive matching
8
matching media
8
brain
6
human
5
clarity
5

Similar Publications

Epilepsy Stands Nearby: A Pilot CT Perfusion Study on Post-Stroke Non-Convulsive Status Epilepticus.

Eur J Neurol

February 2025

IRCCS Istituto delle Scienze Neurologiche di Bologna, Department of Neurology and Stroke Center, Maggiore Hospital, Bologna, Italy.

Background: To investigate the relevance of hyperperfusion on computerised perfusion imaging (CTP) in the emergency setting in people with non-convulsive status epilepticus (NCSE) and previous stroke, to derive relevant aspects on the epileptogenic focus and the network recruited for NCSE propagation.

Methods: We enrolled consecutive adult patients with acute-onset NCSE and a previous stroke at a single institution undergoing CTP and EEG during symptoms. All patients underwent standard imaging including CT, CTP, CT angiograms and standard EEG within 30 min from hospital arrival.

View Article and Find Full Text PDF

Background: Biallelic pathogenic variants in the FUCA1 gene are associated with fucosidosis. This report describes a 4-year-old boy presenting with psychomotor regression, spasticity, and dystonic postures.

Methods And Results: Trio-based whole exome sequencing revealed two previously unreported loss-of-function variants in the FUCA1 gene.

View Article and Find Full Text PDF

Background: Degeneration of the basal forebrain cholinergic system is a hallmark feature shared by Alzheimer's disease (AD) and Lewy body disease (LBD) whereas hippocampus atrophy is more specifically related to AD. We aimed to investigate the relationship between basal forebrain and hippocampus atrophy, cognitive decline, and neuropathology in a large autopsy sample.

Methods: Data were obtained from the National Alzheimer's Coordinating Center (NACC).

View Article and Find Full Text PDF

In this work, we introduce spatial and chemical saturation options for artefact reduction in magnetic resonance fingerprinting (MRF) and assess their impact on T and T mapping accuracy. An existing radial MRF pulse sequence was modified to enable spatial and chemical saturation. Phantom experiments were performed to demonstrate flow artefact reduction and evaluate the accuracy of the T and T maps.

View Article and Find Full Text PDF

Second-generation anti-amyloid monoclonal antibodies for Alzheimer's disease: current landscape and future perspectives.

Transl Neurodegener

January 2025

Department of Biochemistry, College of Medicine, Konyang University, 158, Gwanjeodong-Ro Seo-Gu, Daejeon, 35365, Republic of Korea.

Alzheimer's disease (AD) is the most common type of dementia. Monoclonal antibodies (MABs) serve as a promising therapeutic approach for AD by selectively targeting key pathogenic factors, such as amyloid-β (Aβ) peptide, tau protein, and neuroinflammation. Specifically, based on their efficacy in removing Aβ plaques from the brains of patients with AD, the U.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!