title: The norepinephrine transporter (NET) radioligand (S,S)-[18F]FMeNER-D2 shows significant decreases in NET density in the human brain in Alzheimer's disease: a post-mortem autoradiographic study.
abstract: Earlier post-mortem histological and autoradiographic studies have indicated a reduction of cell numbers in the locus coeruleus (LC) and a corresponding decrease in norepinephrine transporter (NET) in brains obtained from Alzheimer's disease (AD) patients as compared to age-matched healthy controls. In order to test the hypothesis that the regional decrease of NET is a disease specific biomarker in AD and as such, it can be used in PET imaging studies for diagnostic considerations, regional differences in the density of NET in various anatomical structures were measured in whole hemisphere human brain slices obtained from AD patients and age-matched control subjects in a series of autoradiographic experiments using the novel selective PET radioligand for NET (S,S)-[(18)F]FMeNER-D(2). (S,S)-[(18)F]FMeNER-D(2) appears to be a useful imaging biomarker for quantifying the density of NET in various brain structures, including the LC and the thalamus wherein the highest densities are found in physiological conditions. In AD significant decreases of NET densities can be demonstrated with the radioligand in both structures as compared to age-matched controls. The decreases in AD correlate with the progress of the disease as indicated by Braak grades. As the size of the LC is below the spatial resolution of the PET scanners, but the size of the thalamus can be detected with appropriate spatial accuracy in advanced scanners, the present findings confirm our earlier observations with PET that the in vivo imaging of NET with (S,S)-[(18)F]FMeNER-D(2) in the thalamus is viable. Nevertheless, further studies are warranted to assess the usefulness of such an imaging approach for the early detection of changes in thalamic NET densities as a disease-specific biomarker and the possible use of (S,S)-[(18)F]FMeNER-D(2) as a molecular imaging biomarker in AD.
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden. balazs.gulyas@ki.se
authors.forename: Balázs
authors.initials: B
authors.lastname: Gulyás
authors.forename: Damian
authors.initials: D
authors.lastname: Brockschnieder
authors.forename: Sangram
authors.initials: S
authors.lastname: Nag
authors.forename: Elena
authors.initials: E
authors.lastname: Pavlova
authors.forename: Péter
authors.initials: P
authors.lastname: Kása
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Beliczai
authors.forename: Adám
authors.initials: A
authors.lastname: Légrádi
authors.forename: Károly
authors.initials: K
authors.lastname: Gulya
authors.forename: Andrea
authors.initials: A
authors.lastname: Thiele
authors.forename: Thomas
authors.initials: T
authors.lastname: Dyrks
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001345:Autoradiography; D015415:Biomarkers / Q000032:analysis; D001923:Brain Chemistry; D005462:Fluorine Radioisotopes; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006624:Hippocampus / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008125:Locus Coeruleus / Q000737:chemistry / Q000473:pathology; D008875:Middle Aged; D009025:Morpholines / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000032:analysis* / Q000378:metabolism; D049268:Positron-Emission Tomography; D013788:Thalamus / Q000737:chemistry; D016875:tau Proteins / Q000032:analysis
chemical_list: C506462:2-(alpha-(2-fluoromethoxyphenoxy)benzyl)morpholine; D015415:Biomarkers; D005462:Fluorine Radioisotopes; D005904:Glial Fibrillary Acidic Protein; D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins; D016875:tau Proteins