Alzheimer's disease is associated with accumulation of extracellular beta amyloid peptide 42 (Aβ42) which may induce DNA damage and reduce cellular regenerative potential. These effects may be exacerbated under conditions of folate deficiency. The aim of this study was to investigate whether extracellular Aβ42 induces DNA damage and cell death in human peripheral lymphocytes and whether there is an interactive effect between extracellular Aβ42 and folic acid status. Peripheral blood lymphocytes were cultured in medium under conditions of both low and high folate (20 and 200 nM, respectively) and challenged with either Aβ42 or the physiologically normal form Aβ40 (both at 5, 10, 15 µM). Genome stability and cytotoxicity events were investigated using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay. Outcome measures scored included the nuclear division index (NDI), necrosis, apoptosis, binucleated cells with micronuclei (MN), nucleoplasmic bridges (NPB), and nuclear buds (NBUD) and abnormally shaped nuclei (circular, (CIR) and horse-shoe, (HS) that may be indicative of mitotic disruption. Folic acid deficiency significantly reduced NDI (P