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P2–386: Frailty in relation to neuropathological markers of Alzheimer's disease: Evidence from a transgenic mouse model
Author(s) -
Wallace Lindsay,
Howlett Susan,
Reid Andrew,
Darvesh Sultan,
Rockwood Kenneth
Publication year - 2013
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.2013.05.1035
Subject(s) - genetically modified mouse , medicine , amyloid beta , amyloid (mycology) , disease , frailty index , alzheimer's disease , cognitive impairment , endocrinology , gerontology , transgene , pathology , biology , biochemistry , gene
(ACC) connectivity is expected in transgenic (TG) rats, linked to a higher [11 C]PiB retention, representing amyloid-induced neurodegeneration. Methods: A total of ten 18 months-old rats (5 TG, 5 controls) were scanned using Positron Emission Tomography (PET) with [11 C]PiB and task-free fMRI. Outcome measures were BP ND for [11 C]PiB and correlation with a seed-point in the ACC for resting-state fMRI. Results: [11 C]PiB was observed mainly in the thalamus and hippocampus, as well as the anterior cingulate (fig. 1), with global values being higher in TG rats by 10.5% [t(8) 1⁄4 4.25, p1⁄4 0.003)]. In control rats, resting-state activity in the ACC significantly correlates with areas throughout the frontal, parietal and temporal cortices, as well as the ventral horn of the hippocampus (fig. 2). This connectivity is reduced globally in TG rats, where losses in the frontal and entorhinal areas, as well as in the basal ganglia, are strongly predicted by global [11 C]PiB BP ND values (fig. 3), with an average r of -0.7477 (p 1⁄4 0.0329). Additionally, increased [11 C]PiB binding in TG rats is associated with a higher fMRI activity in the dorsal hippocampus. Conclusions: In conclusion, the McGill-R-Thy1-APP rat appears to have a neuroimaging profile of both amyloidosis and neurodegeneration which reflects the pathology seen in the human AD spectrum, including hippocampus hyperactivation which has been observed in MCI.