- Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by neuritic plaques (NPs), and neurofibrillary tangles (NFTs). β-Amyloid peptide 1-4 2 (Aβ(1-42)) is the principal component of NPs and is associated with oxidative stress, as well as dysfunction of cholinergic neurotransmission system and cell death. Nevertheless, one of the most promising therapeutic approaches for patients with AD is based on the pharmacological intervention to increases acetylcholine levels and reduces oxidative stress in AD brain. Previous studies have indicated that alkaloids from Amaryllidaceae family exhibit a wide range of biological activities. The purpose of this study was to investigate whether C. subedentata extract may modulate Aβ(1-42)- induced genotoxicity in SH-SY5Y cell line. Here, we conducted a set of bioassays to measure: viability, clonogenic survival, cell death, chromosome damage and DNA strand breaks. The results showed that Aβ(1-42) significantly inhibited cell viability through necrosis rather than apoptosis, increased the percentage of DNA damage and caused mitochondrial morphological alterations. Treatment with the C. subedentata extract led to a significant recovery of cell survival, decreased necrotic cell death and exerted an induction of antigenotoxic effects; additionally, the extract caigused inhibition of acetylcholinesterase (AChE). The present study confirms neuroprotective activities of C. subedentata belonging Amaryllidaceae family and provide a novel information to clarify the mechanisms by which the extracts decrease DNA damage levels induced by Aβ(1-42).