%0 Journal Article
%T Cholinergic Depletion in Alzheimer¡¯s Disease Shown by [18F]FEOBV Autoradiography
%A Maxime J. Parent
%A Marc-Andre Bedard
%A Arturo Aliaga
%A Luciano Minuzzi
%A Naguib Mechawar
%A Jean-Paul Soucy
%A Esther Schirrmacher
%A Alexey Kostikov
%A Serge G. Gauthier
%A Pedro Rosa-Neto
%J International Journal of Molecular Imaging
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/205045
%X Rationale. Alzheimer¡¯s Disease (AD) is a neurodegenerative condition characterized in part by deficits in cholinergic basalocortical and septohippocampal pathways. [18F]Fluoroethoxybenzovesamicol ([18F]FEOBV), a Positron Emission Tomography ligand for the vesicular acetylcholine transporter (VAChT), is a potential molecular agent to investigate brain diseases associated with presynaptic cholinergic losses. Purpose. To demonstrate this potential, we carried out an [18F]FEOBV autoradiography study to compare postmortem brain tissues from AD patients to those of age-matched controls. Methods. [18F]FEOBV autoradiography binding, defined as the ratio between regional grey and white matter, was estimated in the hippocampus (13 controls, 8 AD) and prefrontal cortex (13 controls, 11 AD). Results. [18F]FEOBV binding was decreased by 33% in prefrontal cortex, 25% in CA3, and 20% in CA1. No changes were detected in the dentate gyrus of the hippocampus, possibly because of sprouting or upregulation toward the resilient glutamatergic neurons of the dentate gyrus. Conclusion. This is the first demonstration of [18F]FEOBV focal binding changes in cholinergic projections to the cortex and hippocampus in AD. Such cholinergic synaptic (and more specifically VAChT) alterations, in line with the selective basalocortical and septohippocampal cholinergic losses documented in AD, indicate that [18F]FEOBV is indeed a promising ligand to explore cholinergic abnormalities in vivo. 1. Introduction Alzheimer¡¯s Disease (AD) is the most prevalent neurodegenerative condition in individuals over 65 [1]. AD neuropathology is characterized by progressive accumulation of amyloid beta peptide (brain amyloidosis), intraneuronal inclusion of hyperphosphorylated tau (neurofibrillary tangles), and degeneration of various neuronal populations. Depletion of cholinergic cell bodies located in the basal forebrain constitutes one of the earliest findings observed in postmortem AD brains [2]. This forebrain neurodegeneration depletes cholinergic projections in virtually the entire prosencephalon. Specifically, degeneration of the Nucleus Basalis of Meynert as well as the medial septum severely perturbs cholinergic neurotransmission at the level of the cortex and hippocampus, respectively [3]. In contrast, cholinergic neurotransmission remains mostly unaffected in other brain regions such as the basal ganglia, thalamus, brainstem, and cerebellum. Quantification of presynaptic terminals provides significant information regarding numerous biochemical processes related to cholinergic neurotransmission.
%U http://www.hindawi.com/journals/ijmi/2013/205045/