Visualizing pathology deposits in the living brain of patients with Alzheimer's disease

Abstract

One of the major neuropathological changes characteristic of Alzheimer's disease (AD) are deposits of beta-amyloid plaques and neurofibrillary tangles in neocortical and subcortical regions of the AD brain. The histochemical detection of these lesions in postmortem brain tissue is necessary for definitive diagnosis of AD. Methods for their in vivo detection would greatly aid the diagnosis of AD in early stages when neuronal loss and related functional impairment are still limited and also open the opportunity for effective therapeutic interventions. Positron emission tomography (PET) using an appropriate radiolabeled imaging probe with high binding affinity for these lesions is one of such techniques. We have developed 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP), a naphthalene-based radiofluorinated PET imaging probe with binding affinity for amyloid and amyloid-like structures, and applied it for in vivo brain imaging of patients with Alzheimer's disease and cognitively normal controls with PET. Analysis of in vivo [F-18]FDDNP imaging data using Logan plot graphical analysis with the cerebellum as a reference region was performed, and the binding levels in several areas of neocortex were determined. We observed increased levels of [F-18]FDDNP binding in patients in several neocortical regions in Alzheimer's disease compared with the cerebellum. In contrast, control subjects have uniformly low levels of [F-18]FDDNP binding in all areas, which is comparable to that of cerebellum.