One of the proteins belonging to the transmembrane 4 superfamily, T-cell acute lymphoblastic leukemia-associated antigen 1 (TALLA1), behaves like a potential tumor-associated antigen. Furthermore, its mRNA is expressed in normal brain. We examined here the histochemical localization of the protein and its mRNA in human brain tissues. Both nonneurological and Alzheimer disease (AD) brains showed astroglial staining for the TALLA1 molecule. In AD brain tissues, globular dystrophic neurites were positively stained. In damaged white matter showing leukoaraiosis by CT scan there was varicose axonal staining with the anti-TALLA1 antibody. In situ hybridization histochemistry using a RNA probe demonstrated neuronal expression of the mRNA. These results suggest that TALLA1, like amyloid precursor protein or chromogranin A, is produced in neurons and transported by axonal flow.