Higher soluble amyloid beta concentration in frontal cortex of young adults than in normal elderly or Alzheimer's disease.

Little is known about the relationship between soluble amyloid beta (Abeta) and age. We have measured soluble and insoluble Abeta by enzyme-linked immunosorbent assay (ELISA) in post-mortem frontal cortex in normal brains (16-95 years) and AD. Insoluble Abeta increased with age, and was significantly higher in Alzheimer's disease (AD) than age-matched controls. However, levels of soluble Abeta declined with age and were significantly greater in younger adults than older adults with or without AD. In AD, insoluble : soluble Abeta ratio was much higher than in age-matched controls. The high levels of soluble Abeta in young adults included oligomeric species of Abeta(1-42). These observations do not preclude Abeta oligomers as neurotoxic mediators of AD but suggest that if they are, the toxicity may be restricted to certain species (eg, beta-pleated protofibrillar species not detected by our assay) or takes decades to manifest. The dramatically increased insoluble : soluble Abeta in AD points to an altered dynamic equilibrium of Abeta 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.