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Altered brain development in an early-onset murine model of Alzheimer's disease.

Neurobiology of aging (2014-10-15)
R Allemang-Grand, J Scholz, J Ellegood, L S Cahill, C Laliberté, P E Fraser, S A Josselyn, J G Sled, J P Lerch
ABSTRACT

Murine models of Alzheimer's disease (AD) have been used to draw associations between atrophy of neural tissue and underlying pathology. In this study, the early-onset TgCRND8 mouse model of AD and littermate controls were scanned longitudinally with in vivo manganese-enhanced MRI (MEMRI) before and after the onset of amyloid plaque deposition at 12 weeks of age. Separate cohorts of mice were scanned at 1 week (ex vivo imaging) and 4 weeks (MEMRI) of age to investigate early life alterations in the brain. Contrary to our expectations, differences in neuroanatomy were found in early post-natal life, preceding plaque deposition by as much as 11 weeks. Many of these differences remained at all imaging time points, suggesting that they were programmed early in life and were unaffected by the onset of pathology. Furthermore, rather than showing atrophy, many regions of the TgCRND8 brain grew at a faster rate compared to controls. These regions contained the greatest density of amyloid plaques and reactive astrocytes. Our findings suggest that pathological processes as well as an alteration in brain development influence the TgCRND8 neuroanatomy throughout the lifespan.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Manganese, powder, ≥99.9% trace metals basis
Sigma-Aldrich
Citrate Concentrated Solution, BioUltra, for molecular biology, 1 M in H2O
Sigma-Aldrich
Manganese(II) chloride tetrahydrate, meets USP testing specifications
Sigma-Aldrich
Citrate Concentrated Solution, BioReagent, suitable for coagulation assays, 4 % (w/v)
Sigma-Aldrich
Citric acid trisodium salt, anhydrous, ≥98% (GC)
Sigma-Aldrich
Manganese, powder, −325 mesh, ≥99% trace metals basis
Manganese, foil, not light tested, 25x25mm, thickness 0.001mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 25x25mm, thickness 0.002mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 25x25mm, thickness 0.003mm, permanent polyester support, 98.7%
Manganese, rod, 10mm, diameter 4.0mm, cast, 99.5%
Manganese, foil, not light tested, 50x50mm, thickness 0.007mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 50x50mm, thickness 0.008mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 50x50mm, thickness 0.009mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 50x50mm, thickness 0.0125mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 50x50mm, thickness 0.01mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 100x100mm, thickness 0.02mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 25x25mm, thickness 0.009mm, permanent polyester support, 98.7%
Manganese, rod, 50mm, diameter 4.0mm, cast, 99.5%
Manganese, foil, not light tested, 50x50mm, thickness 0.006mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 25x25mm, thickness 0.0025mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 50x50mm, thickness 0.02mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 25x25mm, thickness 0.0125mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 50x50mm, thickness 0.05mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 50x50mm, thickness 0.015mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 50x50mm, thickness 0.003mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 100x100mm, thickness 0.01mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 50x50mm, thickness 0.025mm, permanent polyester support, 98.7%
Manganese, foil, not light tested, 25x25mm, thickness 0.007mm, permanent polyester support, 98.7%
Manganese, rod, 50mm, diameter 6.35mm, cast, 99.5%
Manganese, foil, 25x25mm, thickness 2mm, hot-pressed, 99.95%