Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis - Array tomography data

Abstract

We provide the raw array tomography data that was analysed for the publication "Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis", published in Acta Neuropathologica by Henstridge et al. These raw images were taken from human brain samples from two brain regions, primary motor cortex (Brodmann Area 4, or BA4) and frontal cortex (Brodmann Area 9 or BA9). For each human case, we took images from two different samples (blocks) per region, and we imaged 2 image stacks per case. Images for each brain region are included in a separate folder. Each raw image is labeled in a systematic way: Case number - brain region - block number - image number - channel description. The stains used were synaptophysin (syo) to label presynaptic terminals, aw7 to label amyloid beta plaques to ensure that synapse loss was not driven by the presence of amyloid plaques, post-synaptic density 95 (PSD) to label post synapses, pTDP43 to label phosphorylated TDP43 pathology, and DAPI to label nuclei. For the publication, we only included analysis of presynaptic density as the PSD staining was not reliably high enough quality to quantify. Further, we included images of colocalization of pTDP43 with presynaptic markers. For image analysis, we aligned each image stack using multistackreg plugin in Fiji/ImageJ, thresholded the synaptic puncta, and detected the numbers and sizes of the synapses using a watershed programme. Colocalization was determined by a custom in house MATLAB macro. ImageJ and MATLAB macros generated by our lab and used in this study are available at (https://doi.org/10.7488/ds/2268). Details of the analysis can be found in the associated publication and in the protocols paper Kay et al 2013 Nature Protocols (doi: 10.1038/nprot.2013.078). The case numbers and quantification of synapse density can be found in the spreadsheet included with this dataset.