title: The 2,6-disubstituted naphthalene derivative FDDNP labeling reliably predicts Congo red birefringence of protein deposits in brain sections of selected human neurodegenerative diseases.
abstract: Deposition of conformationally altered proteins prominently characterizes pathogenesis and pathomorphology of a number of neurodegenerative disorders. 2-(1-{6-[(2-[F-18]fluoroethyl) (methyl)amino]-2-naphthyl} ethylidene) malononitrile ([F-18]FDDNP), a hydrophobic, viscosity-sensitive, solvent-sensitive, fluorescent imaging probe has been used with positron emission tomography to visualize brain pathology in the living brain of Alzheimer disease (AD) patients. Its non-radiofluorinated analog FDDNP was shown to label senile plaques and neurofibrillary tangles (NFTs) in brain tissue sections. This work aimed at evaluating FDDNP labeling of various protein deposits in fixed, paraffin-embedded brain tissue sections of selected neurodegenerative disorders: AD, cerebral amyloid angiopathy (CAA), transmissible spongiform encephalopathies, progressive supranuclear palsy (PSP), Pick disease (PiD), Parkinson disease, dementia with Lewy bodies, multiple system atrophy (MSA). Cerebral hypertensive vascular hyalinosis (HVH) was used as negative control. Significant agreement between amyloid histochemical properties and FDDNP labeling of the deposits was established. FDDNP labeling showed high positive predictive value for birefringence in senile plaques and NFTs in AD, prion plaques and amyloid deposits in CAA. No FDDNP labeled structures were observed in HVH, PSP, PiD or MSA tissue sections. Our findings may be of significant value for the detection of neuropathological aggregates with [F-18]FDDNP in some of these disorders in the living brain of human subjects.
authors.affiliation: Laboratory for Neural Plasticity and Regeneration, Institute of Pathophysiology, University of Ljubljana, Ljubljana, Slovenia. lojze.smid.jr@mf.uni-lj.si
authors.forename: Lojze M
authors.initials: LM
authors.lastname: Smid
authors.forename: Tomaz D
authors.initials: TD
authors.lastname: Vovko
authors.forename: Mara
authors.initials: M
authors.lastname: Popovic
authors.forename: Andrej
authors.initials: A
authors.lastname: Petric
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kepe
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Barrio
authors.forename: Gaj
authors.initials: G
authors.lastname: Vidmar
authors.forename: Mara
authors.initials: M
authors.lastname: Bresjanac
mesh_terms: D001718:Birefringence; D003224:Congo Red / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D015336:Molecular Probe Techniques; D009281:Naphthalenes / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000378:metabolism*; D009570:Nitriles / Q000737:chemistry; D058225:Plaque, Amyloid / Q000737:chemistry / Q000378:metabolism*; D011237:Predictive Value of Tests; D011877:Radionuclide Imaging; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: C444520:2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile; D005456:Fluorescent Dyes; D005462:Fluorine Radioisotopes; D009281:Naphthalenes; D009419:Nerve Tissue Proteins; D009570:Nitriles; D003224:Congo Red