Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease.
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.
Shoghi-Jadid
Kooresh
K
Division of Nuclear Medicine, UCLA School of Medicine, Los Angeles, CA, USA.
Small
Gary W
GW
Agdeppa
Eric D
ED
Kepe
Vladimir
V
Ercoli
Linda M
LM
Siddarth
Prabha
P
Read
Stephen
S
Satyamurthy
Nagichettiar
N
Petric
Andrej
A
Huang
Sung-Cheng
SC
Barrio
Jorge R
JR
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
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