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P1–013: Impact of amyloid deposition upon cortical and striatal cholinergic interneuronal survival in APPswe/PS1ΔE9 transgenic mice
Author(s) -
Perez Sylvia E.,
Dar Saleem,
Mufson Elliott J.
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.2006.05.388
Subject(s) - choline acetyltransferase , cholinergic , cholinergic neuron , basal forebrain , striatum , genetically modified mouse , hippocampus , cerebral cortex , neuroscience , cholinergic fibers , cortex (anatomy) , acetylcholinesterase , biology , medicine , endocrinology , transgene , dopamine , biochemistry , gene , enzyme
Background: The presence of the amyloid in the hippocampus and cortex which receive their primary cholinergic innervation from acetylcholine containing neurons in the basal forebrain may underlie the selective vulnerability of these long projection cells in Alzheimer’s disease (AD). By contrast, the effect of amyloid (A ) deposition upon the survival of local cholinergic interneurons remains unclear. Objective: To evaluate the impact of A deposition on cholinergic local interneurons we performed qualitative and quantitative analyses of cholinergic cortical and striatal interneurons in young (3-6 months old) and old (10-16 months old) amyloid over expressing APPswe/PS1 E9 transgenic and age-matched wild type mice. Methods: Tissue was immunostained for choline acetyltransferase (ChAT) and histochemcically reacted for acetylcholinesterase (AChE) using the Karnovsky and Roots method. Results: APPswe/ PS1 E9 transgenic mice displayed an age-dependent increase in A deposition in the cortex and striatum as well as ChAT and AChE positive dystrophic neurites in close apposition to A plaques in these structures. Interestingly, the overall distribution and the density of ChAT and AChE positive fibers in the cortex appeared similar in these mutant mice at each age examined. The cortical bipolar intrinsic ChAT positive and AChE negative neurons cortex did not show morphological alterations despite being in close proximity to A plaques. In the striatum there was no detectable cell shrinkage or alteration in ChAT optical density measurements in these cholinergic interneurons in the APPswe/PS1 E9 transgenic compared with wild-type mice. Furthermore, stereologic counts did not reveal changes in number of intrinsic striatal or cortical ChAT-immunoreactive neurons between young and old APPswe/PS1 E9 transgenic compared to wild-type mice. Conclusions: These results suggest that amyloid deposition does not impact the survival of cortical and striatal cholinergic interneurons in APPswe/PS1 E9 transgenic mice.