title: Synaptic proteins predict cognitive decline in Alzheimer's disease and Lewy body dementia.
abstract: Our objective was to compare the levels of three synaptic proteins involved in different steps of the synaptic transmission: Rab3A, SNAP25, and neurogranin, in three common forms of dementia: Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Parkinson's disease dementia.
  
  
  
  A total of 129 postmortem human brain samples were analyzed in brain regional specific manner exploring their associations with morphologic changes and cognitive decline.
  
  
  
  We have observed robust changes reflecting synaptic dysfunction in all studied dementia groups. There were significant associations between the rate of cognitive decline and decreased levels of Rab3 in DLB in the inferior parietal lobe and SNAP25 in AD in the prefrontal cortex. Of particular note, synaptic proteins significantly discriminated between dementia cases and controls with over 90% sensitivity and specificity.
  
  
  
  Our findings suggest that the proposition that synaptic markers can predict cognitive decline in AD, should be extended to Lewy body diseases.
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden. Electronic address: erika.bereczki@ki.se.
authors.forename: Erika
authors.initials: E
authors.lastname: Bereczki
authors.affiliation: King's College London, Wolfson Centre for Age-Related Diseases, London, UK.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Francis
authors.affiliation: King's College London, Wolfson Centre for Age-Related Diseases, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Howlett
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Joana B
authors.initials: JB
authors.lastname: Pereira
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry Sahlgrenska Academy, Gothenburg University, Mölndal, Sweden.
authors.forename: Kina
authors.initials: K
authors.lastname: Höglund
authors.affiliation: AstraZeneca Translational Science Centre at Karolinska Institutet, Solna, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Science for Life laboratory, Solna, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Bogstedt
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Angel
authors.initials: A
authors.lastname: Cedazo-Minguez
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jean-Ha
authors.initials: JH
authors.lastname: Baek
authors.affiliation: Department of Neuropathology, Institute of Pathology, University of Debrecen, Debrecen, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Hortobágyi
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, UK.
authors.forename: Johannes
authors.initials: J
authors.lastname: Attems
authors.affiliation: King's College London, Wolfson Centre for Age-Related Diseases, London, UK.
authors.forename: Clive
authors.initials: C
authors.lastname: Ballard
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Dag
authors.initials: D
authors.lastname: Aarsland
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D003937:Diagnosis, Differential; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D020961:Lewy Body Disease / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D008297:Male; D000073216:Mental Status and Dementia Tests; D015999:Multivariate Analysis; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013569:Synapses / Q000378:metabolism
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins
keywords: Alzheimer's disease; Cognitive impairment; Dementia with Lewy bodies; Neurogranin; Parkinson's disease with dementia; Rab3A; SNAP25; Synaptic dysfunction