Cholinergic forebrain degeneration in the APPswe/PS1ΔE9 transgenic mouse

The impact of Aβ deposition upon cholinergic intrinsic cortical and striatal, as well as basal forebrain long projection neuronal systems was qualitatively and quantitatively evaluated in young (2–6 months) and middle-aged (10–16 months) APPswe/PS1ΔE9 transgenic (tg) mice. Cholinergic neuritic swellings occurred as early as 2–3 months of age in the cortex and hippocampus and 5–6 months in the striatum of tg mice. However, cholinergic neuron number or choline acetyltransferase (ChAT) optical density measurements remained unchanged in the forebrain structures with age in APPswe/PS1ΔE9 tg mice. ChAT enzyme activity decreased significantly in the cortex and hippocampus of middle-aged tg mice. These results suggest that Aβ deposition has age-dependent effects on cortical and hippocampal ChAT fiber networks and enzyme activity, but does not impact the survival of cholinergic intrinsic or long projection forebrain neurons in APPswe/PS1ΔE9 tg mice.