Detection of misfolded Aß oligomers for sensitive biochemical diagnosis of Alzheimer's disease.

ABSTRACT

Alzheimer's disease (AD) diagnosis is hampered by the lack of early, sensitive, and objective laboratory tests. We describe a sensitive method for biochemical diagnosis of AD based on specific detection of misfolded Aß oligomers, which play a central role in AD pathogenesis. The protein misfolding cyclic amplification assay (Aß-PMCA), exploits the functional property of Aß oligomers to seed the polymerization of monomeric Aß. Aß-PMCA allowed detection of as little as 3 fmol of Aß oligomers. Most importantly, using cerebrospinal fluid, we were able to distinguish AD patients from control individuals affected by a variety of other neurodegenerative disorders or nondegenerative neurological diseases with overall sensitivity of 90% and specificity of 92%. These findings provide the proof-of-principle basis for developing a highly sensitive and specific biochemical test for AD diagnosis.