title: Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease.
abstract: The authors used 2-(1-(6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malononitrile ([18F]FDDNP), a hydrophobic radiofluorinated derivative of 2-(1-[6-(dimethylamino)-2-naphthyl]ethylidene)malononitrile (DDNP), in conjunction with positron emission tomography to determine the localization and load of neurofibrillary tangles (NFTs) and beta-amyloid senile plaques (APs) in the brains of living Alzheimer disease (AD) patients. Previous work illustrated the in vitro binding characteristics of [18F]FDDNP to synthetic beta-amyloid(1-40) fibrils and to NFTs and APs in human AD brain specimens. In the present study, greater accumulation and slower clearance was observed in AP- and NFT-dense brain areas and correlated with lower memory performance scores. The relative residence time of the probe in brain regions affected by AD was significantly greater in patients with AD (n=9) than in control subjects (n=7; p=0.0007). This noninvasive technique for monitoring AP and NFT development is expected to facilitate diagnostic assessment of patients with AD and assist in response-monitoring during experimental treatments.
authors.affiliation: Division of Nuclear Medicine, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Kooresh
authors.initials: K
authors.lastname: Shoghi-Jadid
authors.forename: Gary W
authors.initials: GW
authors.lastname: Small
authors.forename: Eric D
authors.initials: ED
authors.lastname: Agdeppa
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kepe
authors.forename: Linda M
authors.initials: LM
authors.lastname: Ercoli
authors.forename: Prabha
authors.initials: P
authors.lastname: Siddarth
authors.forename: Stephen
authors.initials: S
authors.lastname: Read
authors.forename: Nagichettiar
authors.initials: N
authors.lastname: Satyamurthy
authors.forename: Andrej
authors.initials: A
authors.lastname: Petric
authors.forename: Sung-Cheng
authors.initials: SC
authors.lastname: Huang
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Barrio
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D005456:Fluorescent Dyes; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008568:Memory; D008875:Middle Aged; D009281:Naphthalenes; D016874:Neurofibrillary Tangles / Q000000981:diagnostic imaging*; D009483:Neuropsychological Tests; D009570:Nitriles; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals; D014055:Tomography, Emission-Computed / Q000379:methods
chemical_list: C444522:1-(6-((2-fluoroethyl)(methyl)amino)naphthalen-2-yl)ethanone; C444520:2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile; D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D009281:Naphthalenes; D009570:Nitriles; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18