The study is based on the premise that the enzyme lysyl oxidase (LO), which catalyzes the crosslinking of extracellular matrix (ECM) proteins, participates in ECM modulation and senile plaque formation in Alzheimer's disease (AD). Experiments on hippocampal samples indicate that LO activity is increased (about 30%) in AD, but also in non-Alzheimer's dementia, as compared to controls with unrelated diseases. Immunohistochemistry with specific LO antibody indicates localization in blood vessel walls and in plaque-like structures. The number of LO-positive plaque-like structures in AD was over two-fold higher as compared to both non-Alzheimer's dementia and control groups. The findings lead us to suggest that active LO molecules in the ECM may be associated with plaque formation.