{
  "abstract": "Background Beta-synuclein is an emerging blood biomarker for detecting synaptic damage in Alzheimer’s disease (AD) but its role in early AD as well as in other dementias is unclear.Methods We measured with immunoprecipitation mass-spectrometry serum beta-synuclein levels in an exploratory cohort of 80 patients recruited at the University of Perugia (Perugia, Italy) (n=56 AD; n=24 controls) and in a validation cohort of 269 patients recruited at the University of Barcelona (Barcelona, Spain) (n=108 AD; n=53 frontotemporal lobar degeneration (FTLD); n=73 dementia with Lewy bodies and mild cognitive impairment (MCI) with Lewy bodies, together Lewy body disease (LBD); n=27 controls). We tested associations with diagnostic groups, cognitive decline and other cerebrospinal fluid (CSF) and blood markers (phosphorylated tau protein in position 181 (pTau181), neurofilament light chain protein (NfL), glial fibrillar acidic protein (GFAP)).Results Serum beta-synuclein level was progressively increased in the AD continuum across the preclinical, MCI and dementia stages compared with controls and was correlated with serum pTau181 (r=0.710), NfL (r=0.494) and GFAP concentrations (r=0.621, p<0.001 for all). The biomarker showed high accuracy for the discrimination of AD vs controls (area under the curve (AUC): 0.87) and AD-MCI vs non-AD MCI (AUC: 0.96). High serum beta-synuclein level was correlated with lower Mini-Mental State Examination (MMSE) points at baseline (r=−0.461, p<0.001) and associated with MMSE change at follow-up after accounting for age, sex and the time from baseline to last follow-up visit (p=0.006). Serum beta-synuclein level was similar between FTLD and controls, whereas, in LBD, it was higher with AD copathology as evidenced by CSF analysis (p<0.001).Conclusion High serum beta-synuclein level is a promising biomarker for AD-related synaptic damage.",
  "authors": [
    {
      "affiliations": [
        "Department of Neurology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany"
      ],
      "name": "Lorenzo Barba"
    },
    {
      "affiliations": [
        "Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy"
      ],
      "name": "Giovanni Bellomo"
    },
    {
      "affiliations": [
        "Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain",
        "Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain"
      ],
      "name": "Daniel Alcolea"
    },
    {
      "affiliations": [
        "Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy"
      ],
      "name": "Anna L Wojdala"
    },
    {
      "affiliations": [
        "Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy"
      ],
      "name": "Lorenzo Gaetani"
    },
    {
      "affiliations": [
        "Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain",
        "Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain"
      ],
      "name": "Juan Fortea"
    },
    {
      "affiliations": [
        "Department of Neurology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany"
      ],
      "name": "Samir Abu-Rumeileh"
    },
    {
      "affiliations": [
        "Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain",
        "Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain"
      ],
      "name": "Alberto Lleó"
    },
    {
      "affiliations": [
        "Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy"
      ],
      "name": "Lucilla Parnetti"
    },
    {
      "affiliations": [
        "Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain",
        "Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain"
      ],
      "name": "Olivia Belbin"
    },
    {
      "affiliations": [
        "Department of Neurology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany"
      ],
      "name": "Markus Otto"
    },
    {
      "affiliations": [
        "Department of Neurology, University Hospital Ulm, Ulm, Germany",
        "German Center for Neurodegenerative Diseases (DZNE) Ulm, Ulm, Germany"
      ],
      "name": "Patrick Oeckl"
    }
  ],
  "title": "Serum level changes of the synaptic marker beta-synuclein in Alzheimer’s disease continuum and other dementias",
  "uid": "40d5b226-ce0e-58d1-9fd6-410972190c5a"
}