The Alzheimer's amyloid precursor protein (APP) is a type I transmembrane glycoprotein with receptor-like characteristics that originates the Abeta peptide by proteolytic processing. Abeta is potentially cytotoxic and the major component of the cerebral amyloid plaques in Alzheimer's disease (AD) patients. APP is known to be ubiquitously expressed in mammalian cells, with a broad tissue distribution, and Abeta deposition has been reported to occur also in many cells outside the nervous system. Although many putative functions have been suggested for APP, its precise physiological role remains to be elucidated. As several results point to a role of chronic inflammation in AD pathogenesis and suggest that AD might be a systemic disorder, the importance of APP function in non-neuronal cells/tissues has gained increased relevance. Previous studies have shown that amyloid precursor-like protein 2 (APLP2) is highly expressed in testis and sperm, but failed to unambiguously prove the presence of APP itself in mammalian sperm. The use of a battery of available antibodies that detect APP-specific epitopes or epitopes shared with other APP family members, revealed quite distinct distributions in human sperm. Our results are consistent with previous observations of APLP2 in sperm and unequivocally demonstrate the presence of APP itself in human sperm, thus suggesting a putative role for this important protein in sperm function.