Formaldehyde, one of the most toxic organic compounds, is produced and processed in human cells. The level of human endogenous formaldehyde is maintained at a low concentration (0.01-0.08 mmol L(-1) in blood) under physiological conditions, but the concentration increases during ageing (over 65 years old). Clinical trials have shown that urine formaldehyde concentrations are significantly different between elderly Alzheimer's patients (n=91) and normal elderly volunteers (n=38) (P<0.001). Abnormally high levels of intrinsic formaldehyde lead to dysfunction in cognition such as learning decline and memory loss. Excess extracellular and intracellular formaldehyde could induce metabolic response and abnormal modifications of cellular proteins such as hydroxymethylation and hyperphosphorylation, protein misfolding, nuclear translocation and even cell death. This cellular response called formaldehyde stress is dependent upon the concentration of formaldehyde. Chronic impairments of the brain resulted from formaldehyde stress could be one of the mechanisms involved in the process of senile dementia during ageing.