Early Increases in Soluble Amyloid-β Levels Coincide with Cholinergic Degeneration in 3xTg-AD Mice

Accumulation of amyloid-β peptides (Aβ) and cholinergic degeneration are hallmarks of Alzheimer's disease (AD). In a triple transgenic mouse model of AD (3xTg-AD), soluble Aβ42 levels were detected in the septum by 2 months of age, reaching their highest levels at 3-6 months and decreasing at 12 months. Deficits in the number of septal cholinergic neurons and the length of hippocampal cholinergic axons were observed starting at 4 months in 3xTg-AD mice. Our results show that septal Aβ and septohippocampal cholinergic pathology in 3xTg-AD mice occur at an early stage of disease.