Molecular PET imaging for in vivo detection of amyloid in the human brain

Abstract

Neocortical deposition of amyloid plaques is one of the pathological hallmarks of Alzheimer's disease (AD). In vivo detection of amyloid plaques in the brain enables early identification of AD patients. Many β-sheet binding agents have been developed as amyloid-binding radiotracers for PET. Currently, the most successful amyloid-binding agent is 11C-PIB. PET amyloid-imaging studies in human subjects have shown a robust difference between the retention pattern in AD patients and healthy controls. In vivo amyloid-imaging enables early and accurate detection of AD patients in the stage of MCI. The demonstration of abnormal tracer retention in a proportion of the elderly normal subjects supports post mortem observations that the amyloid deposition predominantly occurs before the onset of dementia. For presymptomatic diagnosis of AD, longitudinal studies are needed to elucidate the relation between amyloid deposition and time course of AD. AD and many other neurodegenerative disorders belong to the family of protein misfolding diseases, characterized by protein self-aggregation and deposition. Molecular PET imaging using β-sheet binding agents has the potential to be extended to these wide spectrums of protein misfolding diseases.