A comparative study of growth cone morphology in cultured embryonic neurons derived from wild type PS1(+/+) and knockout PS1(−/−) mice has been performed. Growth cones from wild type PS1(+/+) mice were well spread and usually formed radially continuous and regular lamellar extensions, short filopodia. In contrast, most growth cones from knockout PS1(−/−) mice collapsed after 3–4 days in culture. Summarizing these data, we suggest that PS1 plays an important role in growth cone structure by stabilizing the integrity of the cytoskeleton. The growth cone collapse may be the main reason of abnormal neuronal migration and impaired synaptic function in PS1(−/−) mice.