Different β-amyloid oligomer assemblies in Alzheimer brains correlate with age of disease onset and impaired cholinergic activity

Fuxiang Bao, Linn Wicklund, Pascale N. Lacor, William L. Klein, Agneta Nordberg*, Amelia Marutle

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

In this study, we examined the relationship between various β-amyloid (Aβ) oligomer assemblies in autopsy brain with the levels of fibrillar Aβ and cholinergic synaptic function. Brain tissues obtained from the frontal cortex of 14 Alzheimer's disease (AD) patients grouped into early-onset AD (EOAD) and late-onset AD (LOAD) and 12 age-matched control subjects were used to extract and quantify Aβ oligomers in soluble (TBS), detergent soluble (TBST), and insoluble (GuHCl) fractions. The predominant oligomeric Aβ assemblies detected were dodecamers, decamers, and pentamers, and different patterns of expression were observed between EOAD and LOAD patients. There was no association between any of the detected Aβ oligomer assemblies and fibrillar Aβ levels measured by N-methyl[3H] 2-(40-methylaminophenyl)-6-hydroxy-benzothiazole ([3H]PIB) binding. Levels of pentamers in the soluble fraction significantly correlated with a reduction in choline acetyltransferase activity in AD patients. The number of nicotinic acetylcholine receptors negatively correlated with the total amount of Aβ oligomers in the insoluble fraction in EOAD patients, and with decamers in the soluble fraction in LOAD patients. These novel findings suggest that distinct Aβ oligomers induce impairment of cholinergic neurotransmission in AD pathogenesis.

Original languageEnglish (US)
Pages (from-to)825.e1-825.e13
JournalNeurobiology of Aging
Volume33
Issue number4
DOIs
StatePublished - Apr 2012

Keywords

  • APPswe mutation
  • Age
  • Alzheimer's disease
  • Autopsy brain
  • Choline acetyltransferase activity
  • Early-onset Alzheimer's disease
  • Fibrillar β-amyloid
  • Late-onset Alzheimer's disease
  • Nicotinic acetylcholine receptors
  • β-amyloid oligomers

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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