Cover Story：Dysmetabolism of endogenous formaldehyde is regarded as one of the risk factors for the onset and progression of Alzheimer’s disease. Excess extracellular and intracellular formaldehyde induce neuron death, involving the impairment of cognitive ability. As previously reported, lysosome dysfunction plays an important role in neurodegenerative diseases and intracellular formaldehyde locates in the lysosome. Utilizing formaldehyde fluorescent probe, abnormally increase of the lysosomal formaldehyde was detected in the blood endothelial cell line (bEnd.3) and neuroblastoma N2a cells (N2a) from mouse brain under oxidative stress. Brain formaldehyde was significantly (P < 0.01) elevated in the chronic cerebral hypoperfusion rats compared with those with SHAM. LeuLeuOMe was used to induce the permeabilization of lysosome membrane in bEnd.3. After LeuLeuOMe tretment, higher intracellular and lower extracellular formaldehyde were measured by microplate reader and high performance liquid chromatography (HPLC) respectively. In other words, lysosome not only accommodates endogenous formaldehyde, but also transports the compound out of cells. Abnormal lysosome function causes dysmetabolism of formaldehyde, which is correlated with age-related cognitive impairment.