Neurochemical Research

, Volume 38, Issue 4, pp 797–806 | Cite as

Effect of α-Synuclein on Amyloid β-Induced Toxicity: Relevance to Lewy Body Variant of Alzheimer Disease

  • Rosa Resende
  • Sueli C. F. Marques
  • Elisabete Ferreiro
  • Isaura Simões
  • Catarina R. Oliveira
  • Cláudia M. F. Pereira
Original Paper


Alzheimer’s disease, the most prevalent age-related neurodegenerative disease, is characterized by the presence of extracellular senile plaques composed of amyloid-beta (Aβ) peptide and intracellular neurofibrillary tangles. More than 50 % of Alzheimer’s disease (AD) patients also exhibit abundant accumulation of α-synuclein (α-Syn)-positive Lewy bodies. This Lewy body variant of AD (LBV-AD) is associated with accelerated cognitive dysfunction and progresses more rapidly than pure AD. In addition, it has been suggested that Aβ and α-Syn can directly interact. In this study we investigated the effect of α-Syn on Aβ-induced toxicity in cortical neurons. In order to mimic the intracellular accumulation of α-Syn observed in the brain of LBV-AD patients, we used valproic acid (VPA) to increase its endogenous expression levels. The release of α-Syn from damaged presynaptic terminals that occurs during the course of the disease was simulated by challenging cells with recombinant α-Syn. Our results showed that either VPA-induced α-Syn upregulation or addition of recombinant α-Syn protect primary cortical neurons from soluble Aβ1-42 decreasing the caspase-3-mediated cell death. It was also found that neuroprotection against Aβ-induced toxicity mediated by α-Syn overexpression involves the PI3K/Akt cell survival pathway. Furthermore, recombinant α-Syn was shown to directly interact with Aβ1-42 and to decrease the levels of Aβ1-42 oligomers, which might explain its neuroprotective effect. In conclusion, we demonstrate that either endogenous or exogenous α-Syn can be neuroprotective against Aβ-induced cell death, suggesting a cell defence mechanism during the initial stages of the mixed pathology.


Amyloid-beta peptide (Aβ) α-Synuclein (α-Syn) Alzheimer’s disease (AD) Lewy body variant of Alzheimer’s disease (LBV-AD) 



Alzheimer’s disease



Lewy bodies


Lewy body variant of AD


Bovine serum albumin


[3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide]




Enhanced chemifluorescence




Glycogen synthase kinase-3β


Phenylmethylsulfonyl fluoride


Polyvinylidene difluoride


Sodium dodecyl sulfate


Sodium dodecyl sulfate-polyacrylamide gel




Tris-buffered saline


Tris-buffered saline with tween


Room temperature


Valproic acid



This work was supported by Instituto de Investigação Interdisciplinar (Project reference: III/54/2005), University of Coimbra, Portugal. R Resende’s fellowship: SFRH/BPD/34712/2007.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Rosa Resende
    • 1
  • Sueli C. F. Marques
    • 1
  • Elisabete Ferreiro
    • 1
  • Isaura Simões
    • 1
    • 3
  • Catarina R. Oliveira
    • 1
    • 2
  • Cláudia M. F. Pereira
    • 1
    • 2
  1. 1.Center for Neuroscience and Cell BiologyUniversity of CoimbraCoimbraPortugal
  2. 2.Faculty of MedicineUniversity of CoimbraCoimbraPortugal
  3. 3.Biocant, Biotechnology Innovation CenterCantanhedePortugal

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