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P2–275: A clue to the lack of success of amyloid imaging agents in transgenic mouse models of Alzheimer's disease
Author(s) -
Ye Liang,
Morgenstern Jennifer,
Thompson Paul,
Baker Sharon,
Lamb Jonathan R.,
Lockhart Andrew
Publication year - 2006
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.2006.05.1114
Subject(s) - genetically modified mouse , fibril , rodent , transgene , in vivo , amyloid (mycology) , binding site , chemistry , binding affinities , biophysics , microbiology and biotechnology , biology , biochemistry , receptor , pathology , medicine , genetics , ecology , gene
amyloid senile plaques and tau neurofibrillary tangles, also accumulate in cortical brain regions in patients with mild cognitive impairment (MCI) who are at risk for Alzheimer’s disease. A non-invasive method to determine regional cerebral patterns of these abnormal protein aggregates would facilitate early diagnosis and monitoring of novel treatments to prevent and eliminate their accumulation. Methods: We performed positron emission tomography (PET) scans on 60 subjects (20 cognitively intact controls, 20 with MCI, 20 with Alzheimer’s disease) after intravenous injections of 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl) amino]-2-naphthyl} ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro. Subject groups were age-matched, and clinical assessments and FDDNPPET scans were repeated for 9 subjects (5 controls, 4 MCI subjects) after approximately two years (mean SD 24 5 months). Autopsy follow-up was available on 1 patient with Alzheimer’s disease. Results: Global FDDNP-PET binding (temporal, parietal, posterior cingulate, and frontal average) was lower for the control group compared with the MCI group (P 0.001), which showed lower binding compared with the Alzheimer’s disease group (P 0.001). Higher cognitive test scores correlated inversely with lower FDDNP binding values (P 0.001). At follow-up, subjects who converted from normal cognitive status to MCI or from MCI to Alzheimer’s disease showed regional FDDNP binding increases ranging from 5 to 11 percent, and autopsy follow-up demonstrated high concentrations of plaques and tangles in brain regions with high FDDNP binding. Conclusions: Although previous PET studies have found differences in cerebral amyloid measures when small groups of dementia patients and controls are compared, the present study is the first to describe in vivo cerebral imaging of amyloid and tau deposits in larger subject groups, including patients with MCI, as well as longitudinal clinical and autopsy follow-up. FDDNP-PET differentiates MCI from Alzheimer’s disease and controls and demonstrates increased binding as clinical neurodegeneration progresses. These results point to the potential utility of FDDNP-PET in early, “preclinical” diagnosis, as well as in monitoring interventions designed to prevent or reduce brain amyloid or tau accumulation.