Synaptic markers of cognitive decline in neurodegenerative diseases: A proteomic approach

Erika Bereczki, Rui M. Branca, Paul T. Francis, Joana B. Pereira, Jean Ha Baek, T. Hortobágyi, Bengt Winblad, Clive Ballard, Janne Lehtiö, Dag Aarsland

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

See Attems and Jellinger (doi:10.1093/brain/awx360) for a scientific commentary on this article. Cognitive changes occurring throughout the pathogenesis of neurodegenerative diseases are directly linked to synaptic loss. We used in-depth proteomics to compare 32 post-mortem human brains in the prefrontal cortex of prospectively followed patients with Alzheimer's disease, Parkinson's disease with dementia, dementia with Lewy bodies and older adults without dementia. In total, we identified 10 325 proteins, 851 of which were synaptic proteins. Levels of 25 synaptic proteins were significantly altered in the various dementia groups. Significant loss of SNAP47, GAP43, SYBU (syntabulin), LRFN2, SV2C, SYT2 (synaptotagmin 2), GRIA3 and GRIA4 were further validated on a larger cohort comprised of 92 brain samples using ELISA or western blot. Cognitive impairment before death and rate of cognitive decline significantly correlated with loss of SNAP47, SYBU, LRFN2, SV2C and GRIA3 proteins. Besides differentiating Parkinson's disease dementia, dementia with Lewy bodies, and Alzheimer's disease from controls with high sensitivity and specificity, synaptic proteins also reliably discriminated Parkinson's disease dementia from Alzheimer's disease patients. Our results suggest that these particular synaptic proteins have an important predictive and discriminative molecular fingerprint in neurodegenerative diseases and could be a potential target for early disease intervention.

Original languageEnglish
Pages (from-to)582-595
Number of pages14
JournalBrain
Volume141
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

Fingerprint

Neurodegenerative Diseases
Proteomics
Dementia
Parkinson Disease
Lewy Body Disease
Alzheimer Disease
Proteins
Synaptotagmin II
Brain
Dermatoglyphics
Prefrontal Cortex
Cognitive Dysfunction
Western Blotting
Enzyme-Linked Immunosorbent Assay
Sensitivity and Specificity
Mortality

Keywords

  • Alzheimer's disease
  • cognitive impairment
  • Lewy body dementias
  • mass spectrometry
  • synaptic proteins

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Bereczki, E., Branca, R. M., Francis, P. T., Pereira, J. B., Baek, J. H., Hortobágyi, T., ... Aarsland, D. (2018). Synaptic markers of cognitive decline in neurodegenerative diseases: A proteomic approach. Brain, 141(2), 582-595. https://doi.org/10.1093/brain/awx352

Synaptic markers of cognitive decline in neurodegenerative diseases : A proteomic approach. / Bereczki, Erika; Branca, Rui M.; Francis, Paul T.; Pereira, Joana B.; Baek, Jean Ha; Hortobágyi, T.; Winblad, Bengt; Ballard, Clive; Lehtiö, Janne; Aarsland, Dag.

In: Brain, Vol. 141, No. 2, 01.02.2018, p. 582-595.

Research output: Contribution to journalArticle

Bereczki, E, Branca, RM, Francis, PT, Pereira, JB, Baek, JH, Hortobágyi, T, Winblad, B, Ballard, C, Lehtiö, J & Aarsland, D 2018, 'Synaptic markers of cognitive decline in neurodegenerative diseases: A proteomic approach', Brain, vol. 141, no. 2, pp. 582-595. https://doi.org/10.1093/brain/awx352
Bereczki, Erika ; Branca, Rui M. ; Francis, Paul T. ; Pereira, Joana B. ; Baek, Jean Ha ; Hortobágyi, T. ; Winblad, Bengt ; Ballard, Clive ; Lehtiö, Janne ; Aarsland, Dag. / Synaptic markers of cognitive decline in neurodegenerative diseases : A proteomic approach. In: Brain. 2018 ; Vol. 141, No. 2. pp. 582-595.
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