Using well-characterized monoclonal antibodies which recognize the N-terminus of presenilin 1 (PS1), we examined by immunohistochemistry brain tissues from patients with nonneurological conditions, Alzheimer's disease (AD) and cerebral infarction, as well as normal human liver tissues. The antibodies to PS1 did not reveal any positive staining in nonneurological conditions. In AD, the antibody showed positive staining of intraneuronal neurofibrillary tangles and neuropil threads. In cerebral infarcts, some macrophages were positively stained. In contrast to the C-terminal fragment of PS1, which has been claimed to be present in senile plaques, the N-terminal fragment binds to intracellular and intradendritic pathological structures and may play a role in tau phosphorylation in AD. (C) 1997 Academic Press.