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Although extensive evidence supports the role of β-amyloid (Aβ) in Alzheimer disease (AD), the neurotoxic mechanisms underlying AD pathogenesis are not understood. On the other hand, neuronal loss is the pathologic feature that best correlates with cognitive impairment. We hypothesized that cholinergic neurodegeneration may lead to AA deposition and tested this by inducing selective cholinergic lesions in APPswe/PS1dE9 mice with murine p75^NTR saporin (mu p75-SAP). Intracerebroventricular lesions that removed approximately 50% of cholinergic innervation to the cortex and hippocampus were induced in animals with incipient (~3 months) and marked (~7 months of age) Aβ deposition. Cranial windows were implanted, and Aβ deposition was monitored in vivo using multiphoton microscopy. Deposition of Aβ was increased as soon as 7 days after the lesion, and this effect was maintained up to 3 …