Amyloid-β (Aβ) plaques occur in close apposition to thickened or swollen
cholinergic and galaninergic neurites within the neocortex and hippocampus in
Alzheimer's disease (AD). Despite this observation, the effect of Aβ deposition upon
cholinergic and galaninergic dystrophic neurite formation remains unclear. Therefore, the purpose of this study was to evaluate the interaction between Aβ deposition within the neocortex and hippocampus upon
cholinergic and galaninergic dystrophic neurite formation. Neocortical and hippocampal tissue harvested from 3- and 12-month-old
amyloid-β
protein precursor (AβPP)swe/PS1ΔE9 transgenic (Tg) mice were dual-immunolabeled with
antibodies against either
choline acetyltransferace and Aβ (10D5) or
galanin (Gal) and Aβ. Stereology was used to quantify
amyloid plaques and
cholinergic or galaninergic dystrophic neurites. Plaque number was assessed using the optical fractionator; plaque area was calculated with the Cavalieri estimator, and dystrophic neurite numbers and thickness were manually measured. Neither
amyloid nor dystrophic neuritic profiles were seen in the brains of 3-month-old Tg mice. In contrast, quantitative analysis revealed significantly more plaques in neocortex than hippocampus, with no difference in regional plaque size in 12-month-old Tg mice. Significantly more
cholinergic than galaninergic dystrophic neurites-per-plaque occurred in the neocortex and hippocampus. Additionally,
cholinergic dystrophic neurites were thicker than galaninergic dystrophic neurites in both regions. These data suggest that
amyloid plaque deposition has a greater impact upon
cholinergic than galaninergic dystrophic neurite formation in the neocortex and hippocampus in AβPPswe/PS1ΔE9 Tg mice. These data are also compatible with the hypothesis that
galanin is neuroprotective and reduces dystrophic neurite formation in the face of
amyloid toxicity.