Neurotoxicity Research

, Volume 7, Issue 1–2, pp 69–76 | Cite as

Insoluble α-synuclein in alzheimer’s disease without lewy body formation

  • Melissa Broe
  • Claire E. Shepherd
  • David M. A. Mann
  • Elizabeth A. Milward
  • Wei -Ping Gai
  • Emma Thiel
  • Glenda M. HallidayEmail author


Insoluble α-synuclein plays a central role in Lewy body diseases, with considerable controversy as to whether it plays a similar role in Alzheimer’s disease (AD). We assessed the tissue location and solubility of cortical α-synuclein in AD (without Lewy body formation) compared with controls, using sequential extraction procedures and Western immunoblotting to quantify different α-synuclein species in their different solubility states. Controls had no insoluble cortical α-synuclein and a ratio of soluble :lipid-associated α-synuclein of 1.2 ± 0.1. Total α-synuclein protein was significantly increased in AD and concentrated within the lipidassociated fraction (soluble :lipid ratio 0.9 ± 0.05, soluble:insoluble 1.5 ± 0.1, lipid:insoluble 1.7 ± 0.1) which proved difficult to localize in paraffinembedded tissue. Tissues prepared without lipid extraction revealed α-synuclein-immunoreactivity in the amorphous components of mature cored AD plaques. This lipid-association of α-synuclein in mature AD plaques links this protein with other lipid changes thought to be important in disease pathogenesis.


Alzheimer’s disease Senile plaques α-Synuclein Protein solubility 


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Copyright information

© Springer 2005

Authors and Affiliations

  • Melissa Broe
    • 1
  • Claire E. Shepherd
    • 1
  • David M. A. Mann
    • 2
  • Elizabeth A. Milward
    • 1
  • Wei -Ping Gai
    • 3
  • Emma Thiel
    • 1
  • Glenda M. Halliday
    • 1
    Email author
  1. 1.Prince of Wales Medical Research InstituteUniversity of New South WalesSydneyAustralia
  2. 2.Clinical Neurosciences Research GroupUniversity of Manchester, Greater Manchester Neurosciences Centre, Hope HospitalSalfordUK
  3. 3.Department of Human PhysiologyFlinders University Medical SchoolBedford ParkAustralia

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