Antemortem-Postmortem Correlation of Florbetapir (18F) PET Amyloid Imaging with Quantitative Biochemical Measures of Aß42 but not Aß40.

ABSTRACT

Amyloid imaging demonstrates the in vivo presence of amyloid-ß (Aß) deposits in the aging human brain but it is still unknown which structural forms and modifications of Aß are detected. In Alzheimer's disease, most amyloid deposits are predominantly composed of Aß ending at amino acid residues Val40 or Ala42. It has been reported that Aß40 is largely restricted to neuritic plaques while Aß42 may be deposited in amyloid plaques of all types, and is often the sole component of diffuse plaques. The distinction is important as it is mainly the neuritic plaques that correlate with cognitive impairment while diffuse plaques may be the initial type of Aß deposited. Whether PET amyloid ligands such as florbetapir-18F (Amyvid) are partially or wholly selective for brain deposits of Aß40 or Aß42 is currently unknown. We compared antemortem florbetapir PET cortical/cerebellar signal intensity (SUVr) of 55 subjects with postmortem biochemical (ELISA) measurements employing specific antibodies against Aß40 and Aß42. Spearman's univariable correlations were significant for both Aß40 and Aß42, but were much stronger for Aß42. Multiple linear regression showed significance only for Aß42. These results suggest that florbetapir binds only weakly, if at all, to Aß40. This may be in part due to the higher likelihood for Aß42 to be present in a ß-pleated sheet tertiary structure, or to differences between Aß40 and Aß42 in ß-pleated sheet tertiary or quaternary structure.