The protective function of gamma-enolase was observed also in brains of a mouse model of Alzheimer disease (Tg2576): C-terminally truncated gamma-enolase localized in immediate plaque vicinity and strongly colocalized with cathepsin X, while uncleaved gamma-enolase exhibiting neuroprotective activity, localized in microglia cells in close proximity of senile plaques. Here, ENO2 is linked to early-onset autosomal dominant Alzheimer disease.