alpha-synuclein inclusions in Alzheimer and Lewy body diseases

E B Mukaetova-Ladinska, J Hurt, R Jakes, J Xuereb, W G Honer, C M Wischik

Research output: Contribution to journalArticle

Abstract

alpha-Synuclein has assumed particular neuropathological interest in the light both of its identification as a non-beta-amyloid plaque constituent in Alzheimer disease (AD), and the recent association between dominant inheritance of Parkinson disease (PD) and 2 missense mutations at positions 30 and 53 of the synuclein protein. We report a systematic study of alpha-synuclein, tau, and ubiquitin immunoreactivity in representative neurodegenerative disorders of late life. The alpha-synuclein association with Lewy bodies is variable, peripheral, and is not stable with respect to proteases or acid treatment, whereas there is no association with Pick bodies. Stable patterns of immunoreactivity included neurites and a novel inclusion body. Although there is an overlap between the presence of Lewy bodies and stable a-synuclein immunoreactivity, this is seen only in the presence of concomitant neuropathological features of AD. The novel alpha-synuclein inclusion body identified in pyramidal cells of the medial temporal lobe in particular was found in AD and in the Lewy body variant of AD, and was associated neither with ubiquitin nor tau protein. The inclusion is therefore neither a Lewy body nor a PHF-core body, but may be confused with the Lewy body, particularly in the Lewy body variant of AD. Abnormal processing of alpha-synuclein leading to its deposition in the form of proteolytically stable deposits is a particular feature of the intermediate stages of AD.

Original languageEnglish
Pages (from-to)408-417
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Volume59
Publication statusPublished - 2000

Keywords

  • Alzheimer disease
  • amyloid deposits
  • alpha-synuclein
  • cortical Lewy body disease
  • neurofibrillary changes
  • A-BETA COMPONENT
  • MULTIPLE SYSTEM ATROPHY
  • CENTRAL-NERVOUS-SYSTEM
  • PARKINSONS-DISEASE
  • PRECURSOR PROTEIN
  • GRANULOVACUOLAR DEGENERATION
  • CYTOPLASMIC INCLUSIONS
  • PRESYNAPTIC PROTEIN
  • SYNAPSE LOSS
  • HUMAN BRAIN

Cite this

Mukaetova-Ladinska, E. B., Hurt, J., Jakes, R., Xuereb, J., Honer, W. G., & Wischik, C. M. (2000). alpha-synuclein inclusions in Alzheimer and Lewy body diseases. Journal of Neuropathology and Experimental Neurology, 59, 408-417.