CoChat
Sign Up
Cited by 107

The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.

Comparative profiling of the synaptic proteome from Alzheimer’s disease patients with focus on the APOE genotype

Hesse, Raphael, Hurtado, Maica Llavero, Jackson, Rosemary J., Eaton, Samantha L., Herrmann, Abigail G., Colom-Cadena, Marti, Tzioras, Makis, King, Declan, Rose, Jamie, Tulloch, Jane, McKenzie, Chris-Anne, Smith, Colin, Henstridge, Christopher M., Lamont, Douglas, Wishart, Thomas M., Spires-Jones, Tara L.·2019·Acta Neuropathologica Communications
DOI 10.1186/s40478-019-0847-7PMC PMC6925519

Published version of a preprint

Open this paper in CoChat — free account

Abstract

Degeneration of synapses in Alzheimer’s disease (AD) strongly correlates with cognitive decline, and synaptic pathology contributes to disease pathophysiology. We recently observed that the strongest genetic risk factor for sporadic AD, apolipoprotein E epsilon 4 ( APOE 4), is associated with exacerbated synapse loss and synaptic accumulation of oligomeric amyloid beta in human AD brain. To begin to understand the molecular cascades involved in synapse loss in AD and how this is mediated by APOE , and to generate a resource of knowledge of changes in the synaptic proteome in AD, we conducted a proteomic screen and systematic in silico analysis of synaptoneurosome preparations from temporal and occipital cortices of human AD and control subjects with known APOE gene status. We examined brain tissue from 33 subjects (7–10 per group). We pooled tissue from all subjects in each group for unbiased proteomic analyses followed by validation with individual case samples. Our analysis identified over 5500 proteins in human synaptoneurosomes and highlighted disease, brain region, and APOE-associated changes in multiple molecular pathways including a decreased abundance in AD of proteins important for synaptic and mitochondrial function and an increased abundance of proteins involved in neuroimmune interactions and intracellular signaling.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s40478-019-0847-7

Cites

20 of 20 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 41

  1. Andreev VP, Petyuk VA, Brewer HM, Karpievitch YV, Xie F, Clarke J, Camp D, Smith RD, Lieberman AP, Albin RL et al (2012) Label-free quantitative LC-MS proteomics of Alzheimer's disease and normally aged human brains. J Proteome Res 11:3053–3067. https://doi.org/10.1021/pr3001546 · DOI
  2. Arold S, Sullivan P, Bilousova T, Teng E, Miller CA, Poon WW, Vinters HV, Cornwell LB, Saing T, GM C et al (2012) Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer's disease and apoE TR mouse cortex. Acta Neuropathol 123:39–52. https://doi.org/10.1007/s00401-011-0892-1 · DOI
  3. Baglietto-Vargas D, Prieto GA, Limon A, Forner S, Rodriguez-Ortiz CJ, Ikemura K, Ager RR, Medeiros R, Trujillo-Estrada L, Martini AC et al (2018) Impaired AMPA signaling and cytoskeletal alterations induce early synaptic dysfunction in a mouse model of Alzheimer's disease Aging Cell:e12791. https://doi.org/10.1111/acel.12791 · DOI
  4. Bayes A, Collins MO, Galtrey CM, Simonnet C, Roy M, Croning MD, Gou G, van de Lagemaat LN, Milward D, Whittle IR et al (2014) Human post-mortem synapse proteome integrity screening for proteomic studies of postsynaptic complexes. Mol Brain 7:88. https://doi.org/10.1186/s13041-014-0088-4 · DOI
  5. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 261:921–923 · DOI · Paper page
  6. Cox J, Mann M (2008) MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol 26:1367–1372. https://doi.org/10.1038/nbt.1511 · DOI · Paper page
  7. Cox J, Neuhauser N, Michalski A, Scheltema RA, Olsen JV, Mann M (2011) Andromeda: a peptide search engine integrated into the MaxQuant environment. J Proteome Res 10:1794–1805. https://doi.org/10.1021/pr101065j · DOI
  8. DeKosky ST, Scheff SW, Styren SD (1996) Structural correlates of cognition in dementia: quantification and assessment of synapse change. Neurodegeneration 5:417–421 · DOI · Paper page
  9. Graham LC, Eaton SL, Brunton PJ, Atrih A, Smith C, Lamont DJ, Gillingwater TH, Pennetta G, Skehel P, Wishart TM (2017) Proteomic profiling of neuronal mitochondria reveals modulators of synaptic architecture. Mol Neurodegener 12:77. https://doi.org/10.1186/s13024-017-0221-9 · DOI
  10. Graham LC, Naldrett MJ, Kohama SG, Smith C, Lamont DJ, McColl BW, Gillingwater TH, Skehel P, Urbanski HF, Wishart TM (2019) Regional molecular mapping of primate synapses during normal healthy ageing. Cell Rep 27 (1018-1026):e1014. https://doi.org/10.1016/j.celrep.2019.03.096 · DOI
  11. Henstridge CM, Sideris DI, Carroll E, Rotariu S, Salomonsson S, Tzioras M, McKenzie CA, Smith C, von Arnim CAF, Ludolph ACet al (2018) Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis. Acta Neuropathol 135: 213–226 Doi https://doi.org/10.1007/s00401-017-1797-4 · DOI
  12. Henstridge CM, Spires-Jones T (2019) Beyond the neuron - cellular interactions early in Alzheimer’s disease pathogenesis. Nat Rev Neurosci · DOI · Paper page
  13. Hesse R, von Einem B, Wagner F, Bott P, Schwanzar D, Jackson RJ, Föhr KJ, Lausser L, Kroker KS, Proepper C et al (2018) sAPPβ and sAPPα increase structural complexity and E/I input ratio in primary hippocampal neurons and alter Ca. Exp Neurol 304:1–13. https://doi.org/10.1016/j.expneurol.2018.02.010 · DOI
  14. Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57. https://doi.org/10.1038/nprot.2008.211 · DOI · Paper page
  15. Izzo NJ, Xu J, Zeng C, Kirk MJ, Mozzoni K, Silky C, Rehak C, Yurko R, Look G, Rishton Get al (2014) Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity. PLoS One 9: e111899 Doi https://doi.org/10.1371/journal.pone.0111899 · DOI · Paper page
  16. Jackson RJ, Rose J, Tulloch J, Henstridge C, Smith C, Spires-Jones TL (2019) Clusterin accumulates in synapses in Alzheimer’s disease and is increased in apolipoprotein E4 carriers. Brain Commun 1. https://doi.org/10.1093/braincomms/fcz003 · DOI · Paper page
  17. Jones RA, Harrison C, Eaton SL, Llavero Hurtado M, Graham LC, Alkhammash L, Oladiran OA, Gale A, Lamont DJ, Simpson H et al (2017) Cellular and molecular anatomy of the human neuromuscular junction. Cell Rep 21:2348–2356. https://doi.org/10.1016/j.celrep.2017.11.008 · DOI
  18. Kay KR, Smith C, Wright AK, Serrano-Pozo A, Pooler AM, Koffie R, Bastin ME, Bak TH, Abrahams S, Kopeikina KJ et al (2013) Studying synapses in human brain with array tomography and electron microscopy. Nat Protoc 8:1366–1380. https://doi.org/10.1038/nprot.2013.078 · DOI · Paper page
  19. Kvartsberg H, Duits FH, Ingelsson M, Andreasen N, Ohrfelt A, Andersson K, Brinkmalm G, Lannfelt L, Minthon L, Hansson O et al (2015) Cerebrospinal fluid levels of the synaptic protein neurogranin correlates with cognitive decline in prodromal Alzheimer's disease. Alzheimers Dement 11:1180–1190. https://doi.org/10.1016/j.jalz.2014.10.009 · DOI
  20. Litvinchuk A, Wan YW, Swartzlander DB, Chen F, Cole A, Propson NE, Wang Q, Zhang B, Liu Z, Zheng H (2018) Complement C3aR inactivation attenuates tau pathology and reverses an immune network deregulated in Tauopathy models and Alzheimer's disease. Neuron: Doi. https://doi.org/10.1016/j.neuron.2018.10.031 · DOI · Paper page
  21. Llavero Hurtado M, Fuller HR, Wong AMS, Eaton SL, Gillingwater TH, Pennetta G, Cooper JD, Wishart TM (2017) Proteomic mapping of differentially vulnerable pre-synaptic populations identifies regulators of neuronal stability in vivo. Sci Rep 7:12412. https://doi.org/10.1038/s41598-017-12603-0 · DOI
  22. Lleó A, Núñez-Llaves R, Alcolea D, Chiva C, Balateu-Paños D, Colom-Cadena M, Gomez-Giro G, Muñoz L, Querol-Vilaseca M, Pegueroles Jet al (2019) Changes in synaptic proteins precede Neurodegeneration markers in preclinical Alzheimer's disease cerebrospinal fluid. Molecular & Cellular Proteomics 18: 546–560 Doi https://doi.org/10.1074/mcp.RA118.001290 · DOI · Paper page
  23. Manczak M, Kandimalla R, Fry D, Sesaki H, Reddy PH (2016) Protective effects of reduced dynamin-related protein 1 against amyloid beta-induced mitochondrial dysfunction and synaptic damage in Alzheimer's disease. Hum Mol Genet 25:5148–5166. https://doi.org/10.1093/hmg/ddw330 · DOI
  24. Mauricio R, Benn C, Davis J, Dawson G, Dawson LA, Evans A, Fox N, Gallacher J, Hutton M, Isaac Jet al (2019) Tackling gaps in developing life-changing treatments for dementia. Alzheimers Dement (N Y) 5: 241–253 Doi https://doi.org/10.1016/j.trci.2019.05.001 · DOI
  25. McGorum BC, Pirie RS, Eaton SL, Keen JA, Cumyn EM, Arnott DM, Chen W, Lamont DJ, Graham LC, Llavero Hurtado Met al (2015) Proteomic profiling of cranial (superior) cervical ganglia reveals Beta-amyloid and ubiquitin proteasome system perturbations in an equine multiple system neuropathy. Mol Cell Proteomics 14: 3072–3086 Doi https://doi.org/10.1074/mcp.M115.054635 · DOI
  26. Molinari N, Roche S, Peoc'h K, Tiers L, Seveno M, Hirtz C, Lehmann S (2018) Sample pooling and inflammation linked to the false selection of biomarkers for neurodegenerative diseases in top-down proteomics: a pilot study. Front Mol Neurosci 11:477. https://doi.org/10.3389/fnmol.2018.00477 · DOI
  27. Musunuri S, Wetterhall M, Ingelsson M, Lannfelt L, Artemenko K, Bergquist J, Kultima K, Shevchenko G (2014) Quantification of the brain proteome in Alzheimer's disease using multiplexed mass spectrometry. J Proteome Res 13:2056–2068. https://doi.org/10.1021/pr401202d · DOI
  28. Perez-Riverol Y, Csordas A, Bai J, Bernal-Llinares M, Hewapathirana S, Kundu DJ, Inuganti A, Griss J, Mayer G, Eisenacher M et al (2019) The PRIDE database and related tools and resources in 2019: improving support for quantification data. Nucleic Acids Res 47:D442–D450. https://doi.org/10.1093/nar/gky1106 · DOI
  29. Pickett EK, Rose J, McCrory C, McKenzie CA, King D, Smith C, Gillingwater TH, Henstridge CM, Spires-Jones TL (2018) Region-specific depletion of synaptic mitochondria in the brains of patients with Alzheimer's disease. Acta Neuropathol 136:747–757. https://doi.org/10.1007/s00401-018-1903-2 · DOI
  30. Portelius E, Olsson B, Hoglund K, Cullen NC, Kvartsberg H, Andreasson U, Zetterberg H, Sandelius A, Shaw LM, VMY L et al (2018) Cerebrospinal fluid neurogranin concentration in neurodegeneration: relation to clinical phenotypes and neuropathology. Acta Neuropathol 136:363–376. https://doi.org/10.1007/s00401-018-1851-x · DOI
  31. Reddy PH, Beal MF (2008) Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease. Trends Mol Med 14:45–53. https://doi.org/10.1016/j.molmed.2007.12.002 · DOI · Paper page
  32. Reinders NR, Pao Y, Renner MC, da Silva-Matos CM, Lodder TR, Malinow R, Kessels HW (2016) Amyloid-beta effects on synapses and memory require AMPA receptor subunit GluA3. Proc Natl Acad Sci U S A 113:E6526–E6534. https://doi.org/10.1073/pnas.1614249113 · DOI
  33. Spires-Jones TL, Hyman BT (2014) The intersection of amyloid beta and tau at synapses in Alzheimer's disease. Neuron 82:756–771. https://doi.org/10.1016/j.neuron.2014.05.004 · DOI · Paper page
  34. Tai HC, Serrano-Pozo A, Hashimoto T, Frosch MP, Spires-Jones TL, Hyman BT (2012) The synaptic accumulation of hyperphosphorylated tau oligomers in Alzheimer disease is associated with dysfunction of the ubiquitin-proteasome system. Am J Pathol 181:1426–1435. https://doi.org/10.1016/j.ajpath.2012.06.033 · DOI · Paper page
  35. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R (1991) Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30:572–580 · DOI · Paper page
  36. Tzioras M, Davies C, Newman A, Jackson R, Spires-Jones T (2019) Invited review: APOE at the interface of inflammation, neurodegeneration and pathological protein spread in Alzheimer's disease. Neuropathol Appl Neurobiol 45:327–346. https://doi.org/10.1111/nan.12529 · DOI · Paper page
  37. Wang S, Yang F, Petyuk VA, Shukla AK, Monroe ME, Gritsenko MA, Rodland KD, Smith RD, Qian WJ, Gong CX et al (2017) Quantitative proteomics identifies altered O-GlcNAcylation of structural, synaptic and memory-associated proteins in Alzheimer's disease. J Pathol 243:78–88. https://doi.org/10.1002/path.4929 · DOI
  38. WHO (2017) Dementia, a global health priority. World Health Organisation, City
  39. Wishart TM, Paterson JM, Short DM, Meredith S, Robertson KA, Sutherland C, Cousin MA, Dutia MB, Gillingwater TH (2007) Differential proteomics analysis of synaptic proteins identifies potential cellular targets and protein mediators of synaptic neuroprotection conferred by the slow Wallerian degeneration (Wlds) gene. Mol Cell Proteomics 6:1318–1330. https://doi.org/10.1074/mcp.M600457-MCP200 · DOI
  40. Wu H-Y, Kuo P-C, Wang Y-T, Lin H-T, Roe AD, Wang BY, Han C-L, Hyman BT, Chen Y-J, Tai H-C (2018) β-Amyloid induces pathology-related patterns of tau hyperphosphorylation at synaptic terminals. J Neuropathol Exp Neurol 77:814–826. https://doi.org/10.1093/jnen/nly059 · DOI
  41. Zhang Q, Ma C, Gearing M, Wang PG, Chin LS, Li L (2018) Integrated proteomics and network analysis identifies protein hubs and network alterations in Alzheimer's disease. Acta Neuropathol Commun 6:19. https://doi.org/10.1186/s40478-018-0524-2 · DOI · Paper page

Cited by

Sorted by citations

Metadata

Authors
Hesse, R., Hurtado, M. L., Jackson, R. J., Eaton, S. L., Herrmann, A. G., Colom-Cadena, M., Tzioras, M., King, D., Rose, J., Tulloch, J., McKenzie, C.-A., Smith, C., Henstridge, C. M., Lamont, D., Wishart, T. M., & Spires-Jones, T. L.
ORCID
Spires-Jones, Tara L.
Venue
Acta Neuropathologica Communications
Publisher
Springer Science and Business Media LLC
Published
2019-12
Volume
7
Issue
1
ISSN
2051-5960
DOI
10.1186/s40478-019-0847-7
PMC
PMC6925519
Cited by
107
References
20
Language
en
Licence
Funders
  • H2020 European Research Council (681181)
  • Alzheimer's Society (AS-PG-15b-023)
  • UK Dementia Research Institute

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review