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Single-synapse analyses of Alzheimer’s disease implicate pathologic tau, DJ1, CD47, and ApoE

Citation

Phongpreecha, Thanaphong et al. (2021), Single-synapse analyses of Alzheimer’s disease implicate pathologic tau, DJ1, CD47, and ApoE, Dryad, Dataset, https://doi.org/10.5061/dryad.z612jm6cr

Abstract

Synaptic molecular characterization is limited for Alzheimer’s disease (AD). Our newly invented mass cytometry-based method, Synaptometry by Time of Flight (SynTOF), was used to measure 38 antibody probes in approximately 17 million single-synapse events from human brains without pathologic change or with pure AD or Lewy body disease (LBD), non-human primates (NHP), and PS/APP mice. Synaptic molecular integrity in humans and NHP was similar. Although not detected in human synapses, Aβ was in PS/APP mice single-synapse events. Clustering and pattern identification of human synapses showed expected disease-specific differences, like increased hippocampal pathologic tau in AD and reduced caudate dopamine transporter in LBD, and revealed novel findings including increased hippocampal CD47 and lowered DJ1 in AD and higher ApoE in AD with dementia. Our results were independently supported by multiplex ion beam imaging of intact tissue. This highlights the higher depth and breadth of insight on neurodegenerative diseases obtainable through SynTOF.

Methods

The dataset was collected using mass cytometry at The Human Immune Monitoring Center (HIMC) and multiplexed ion beam imaging by time of flight (MIBI-TOF) at Stanford University in 2019-2020 and 2020, respectively. The single-synapse data has been processed by arcsinh transformed with a cofactor of 5 to produce the results published in the BioRxiv, where a detailed experimental method and preprocessing can be found, and is currently under consideration at Science Advances.

Usage Notes

The readme file contains an explanation of each of the metadata of each file (both SynTOF and MIBI-TOF) as well as the column and value descriptions. Information on how the measurements were done can be found in the associated manuscript referenced above. We have also attached scripts we used to generate the results presented in the paper. The explanation of each of the script file is written in readme-files within the zip folder.

Funding

National Institutes of Health, Award: AG057707

National Institutes of Health, Award: AG068279