Single-synapse analyses of Alzheimers disease implicate pathologic tau, DJ1, CD47, and ApoE

Thanaphong Phongpreecha; Chandresh R. Gajera; Candace C. Liu; Kausalia Vijayaragavan; Alan Lee Chang; Martin Becker; Ramin Fallahzadeh; Rosemary Fernandez; Nadia O. Postupna; Emily Sherfield; Dmitry Tebaykin; Caitlin S. Latimer; Carol A. Shively; Thomas C. Register; Suzanne Craft; Kathleen S. Montine; Edward J. Fox; Kathleen L. Poston; Christopher Dirk Keene; Michael Angelo; Sean C. Bendall; Nima Aghaeepour; Thomas Jude Montine

doi:10.1126/sciadv.abk0473

NeuroscienceScience AdvancesDec 15, 2021

Peer-reviewed journal article

Single-synapse analyses of Alzheimers disease implicate pathologic tau, DJ1, CD47, and ApoE

Thanaphong Phongpreecha iD, Chandresh R. Gajera iD, Candace C. Liu iD, Kausalia Vijayaragavan iD, Alan Lee Chang iD, Martin Becker iD, Ramin Fallahzadeh iD, Rosemary Fernandez iD, Nadia O. Postupna iD, Emily Sherfield, Dmitry Tebaykin iD, Caitlin S. Latimer iD, Carol A. Shively iD, Thomas C. Register iD, Suzanne Craft iD, Kathleen S. Montine iD, Edward J. Fox iD, Kathleen L. Poston iD, Christopher Dirk Keene iD, Michael Angelo iD, Sean C. Bendall iD, Nima Aghaeepour iD, Thomas Jude Montine iD

Abstract

Synaptic molecular characterization is limited for Alzheimers disease (AD). We used mass cytometry to quantify 38 probes in approximately 17 million single synaptic 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, A{beta} was in PS/APP mice synaptic 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 dementia. Our results were independently supported by multiplex ion beam imaging of intact tissue.

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