Single-synapse analyses of Alzheimer's disease implicate pathologic tau, DJ1, CD47, and ApoE.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
17 Dec 2021
17 Dec 2021
Historique:
entrez:
15
12
2021
pubmed:
16
12
2021
medline:
16
12
2021
Statut:
ppublish
Résumé
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), nonhuman primates (NHPs), 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 previously unidentified 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.
Identifiants
pubmed: 34910503
doi: 10.1126/sciadv.abk0473
pmc: PMC8673771
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabk0473Subventions
Organisme : NIA NIH HHS
ID : L30 AG074138
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066515
Pays : United States
Organisme : NIA NIH HHS
ID : UF1 AG057707
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM138353
Pays : United States
Organisme : NIA NIH HHS
ID : R24 AG073199
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072947
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL087103
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG056287
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG057915
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL122393
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG068279
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG058829
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG049638
Pays : United States
Organisme : NINDS NIH HHS
ID : P50 NS062684
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066509
Pays : United States
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