133 - Matrin3 Pathology in ALS and Other Neurodegenerative Diseases

Poster Board Number: 133
There are separate poster presentation times for odd and even posters.
Odd poster #s – first hour
Even poster #s – second hour

Abstract Body : Introduction
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscle weakness and atrophy as motor neurons within the brain and spinal cord deteriorate. ALS affects many areas of the central nervous system including distinct regions of the brain, brain stem, spinal cord, and motor neurons. ALS currently has no known cause or cure, though altered proteins are found in many cases. Frontotemporal dementia (FTD) is a disease resulting from the degeneration of neurons in the frontal and temporal lobes. Previously, it was thought that ALS and FTD were separate neurodegenerative diseases that shared various overlapping symptoms. However, the discovery of overlapping pathology and genetic features, it is more likely that ALS and FTD are different presentations of the same neurodegenerative disease. Various proteins have been implicated in ALS pathology such as TDP-43, a well-established hallmark, and Matrin3. Matrin3 is an RNA-binding protein normally localized within the nucleus of cells, with some diffuse staining often present in the cytoplasm. Previous research has suggested that localization and density of Matrin3 are altered in ALS cases. The main objective of the current research is to determine if Matrin3 pathology can be used as a pathological hallmark in the diagnosis of ALS using immunohistochemistry (IHC) by comparing localization of Matrin3 in ALS and neurologically unaffected specimens. A secondary objective is to expand specimens to include sections of frontal and temporal lobes, contributing to the establishment of a potential link between ALS and FTD.

Methods
Tissue specimens sourced from various institutions were analyzed using IHC and bright field microscopy. The tissue specimens were taken from both individuals diagnosed with ALS and neurologically unaffected individuals. Tissue types include spinal cord, frontal lobe, and hippocampus (temporal lobe). Data was quantified using QuPath®, a bioimage analysis software. This program was used to overlay a grid onto a whole slide image and flag neurons with different markers to count all visible neurons and those determined positive for Matrin3 pathology.

Results
Preliminary results (n=5, 1 control, spinal cord tissue) have demonstrated differences in the localization and density of Matrin3 in ALS versus control specimens. A total of 448 neurons were observed in the control specimen with an average reduction of 73.5% of neurons in ALS specimens. A mean of 118.7 neurons were observed in the ALS specimens with an average of 28.1% determined positive for Matrin3 pathology. Immunohistochemical analysis and imaging are still ongoing. Statistical analyses will be completed as more data becomes available.

Discussion
Current results suggest that Matrin3 is altered in ALS cases and can be used as a pathological hallmark in the diagnosis of ALS. Once frontal and temporal lobe specimens are quantified, Matrin3 pathology may also be found in these regions. These results would provide further evidence of a common disease spectrum between ALS and FTD. Further data is needed to confirm these results. Since much is still unknown about Matrin3, future research should use alternate methods to investigate its potential mechanistic role is ALS pathology and determine if it could be used in novel treatment avenues.