These authors contributed equally to this manuscript
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Higher Soluble Amyloid β Concentration in Frontal Cortex of Young Adults than in Normal Elderly or Alzheimer's Disease
Article first published online: 12 JAN 2010
DOI: 10.1111/j.1750-3639.2010.00374.x
© 2010 The Authors; Journal Compilation © 2010 International Society of Neuropathology
Additional Information
How to Cite
Van Helmond, Z., Miners, J. S., Kehoe, P. G. and Love, S. (2010), Higher Soluble Amyloid β Concentration in Frontal Cortex of Young Adults than in Normal Elderly or Alzheimer's Disease. Brain Pathology, 20: 787–793. doi: 10.1111/j.1750-3639.2010.00374.x
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These authors contributed equally to this manuscript
Publication History
- Issue published online: 7 JUN 2010
- Article first published online: 12 JAN 2010
- Received 15 October 2009; accepted 5 January 2010.
Keywords:
- Alzheimer's disease;
- normal aging;
- oligomeric Aβ;
- soluble Aβ
Abstract
Little is known about the relationship between soluble amyloid β (Aβ) and age. We have measured soluble and insoluble Aβ by enzyme-linked immunosorbent assay (ELISA) in post-mortem frontal cortex in normal brains (16–95 years) and AD. Insoluble Aβ increased with age, and was significantly higher in Alzheimer's disease (AD) than age-matched controls. However, levels of soluble Aβ declined with age and were significantly greater in younger adults than older adults with or without AD. In AD, insoluble : soluble Aβ ratio was much higher than in age-matched controls. The high levels of soluble Aβ in young adults included oligomeric species of Aβ1-42. These observations do not preclude Aβ oligomers as neurotoxic mediators of AD but suggest that if they are, the toxicity may be restricted to certain species (eg, β-pleated protofibrillar species not detected by our assay) or takes decades to manifest. The dramatically increased insoluble : soluble Aβ in AD points to an altered dynamic equilibrium of Aβ in AD, reflecting both enhanced aggregation and continued overproduction or impaired removal of the soluble peptide in older age, when the concentration of this peptide should be declining.