Single-synapse analyses of Alzheimer's disease implicate pathologic tau, DJ1, CD47, and ApoE
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Phongpreecha, Thanaphong1
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Gajera, Chandresh1
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Liu, Candace1
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Vijayaragavan, Kausalia1
- Chang, Alan1
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Becker, Martin1
- Fallahzadeh, Ramin1
- Fernandez, Rosemary1
- Postupna, Nadia2
- Sherfield, Emily2
- Tebaykin, Dmitry2
- Latimer, Caitlin2
- Shively, Carol3
- Register, Thomas3
- Craft, Suzanne3
- Montine, Kathleen1
- Fox, Edward1
- Poston, Kathleen1
- Keene, C. Dirk2
- Angelo, Michael1
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Bendall, Sean1
- Aghaeepour, Nima1
- Montine, Thomas1
- 1. Stanford University
- 2. University of Washington
- 3. Wake Forest University
Description
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.
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 provided by: National Institute on Aging
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000049
Award Number: AG057707
Funding provided by: National Institute on Aging
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000049
Award Number: AG068279
Files
Scripts_SynTOF2021-MIBI_part.zip
Additional details
Related works
- Is cited by
- 10.1101/2021.06.14.448240 (DOI)
- Is source of
- 10.5061/dryad.z612jm6cr (DOI)