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P2‐026: Reduced frontal oxygenation during a verbal fluency test in patients suffering from Alzheimer's disease
Author(s) -
B. M. Langer Julia,
Schecklmann Martin,
Polak Thomas T.,
Leonhard Christine,
Leitner Thomas,
Rothenhoefer Martina,
Fallgatter Andreas J.
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.335
Subject(s) - verbal fluency test , audiology , prefrontal cortex , neuropsychology , psychology , dorsolateral prefrontal cortex , fluency , medicine , neuroscience , cognition , mathematics education
Background: The presence of b-amyloid plaques in brain is a hallmark of Alzheimer’s disease (AD) and serves as a biomarker for confirmation of diagnosis postmortem. Positron Emission Tomography (PET) radioligands that binds selectively to b-amyloid are promising new tools supporting the clinical diagnoses of AD. In addition, such methodology may be useful for evaluation of new drugs aiming at reduction of amyloid plaque load. Methods: We have utilized 1) in vitro binding to b-amyloid fibrils as well as cortical sections from human AD brain, 2) ex vivo binding data in aged tg2576 mice after i.v. administration and 3) PET studies in cynomolgus monkeys, to describe the properties of this new PET ligand. Results: Here we describe a new radioligand (AZD4694) with high affinity for b-amyloid fibrils in vitro (Kd 2.3 6 0.3 nM). In cortical sections from human AD brain [H]AZD4694 selectively labelled b-amyloid deposits in gray matter with low level of non-specific binding to plaque devoid white matter. Ex vivo binding data in aged tg2576 mice after intravenous administration showed that [H]AZD4694 selectively labelled b-amyloid plaques with a low levels of nonspecific binding. Congo red labelling in adjacent sections from the same individual showed that [H]AZD4694 and congo red labeled apparently identical structures. The suitability of [F]AZD4694 as a potential PET radioligand was demonstrated further in cynomolgus monkeys. [F]AZD4694 rapidly entered the monkey brain with an exposure of about 5 % of the total injected dose. Brain uptake of [F]AZD4694 peaked within two minutes after injection whereafter brain radioactivity rapidly cleared reaching a homogenous low level after 50 min. Conclusions: Taken together, the preclinical profile of AZD4694 suggests that fluorine-18 labelled AZD4694 may have potential for PET-visualization of b-amyloid deposits in the living human brain.