With increasing longevity, the number of older schizophrenic patients is growing. Previous criteria used the age of symptom onset to differentiate between the late manifestations of early-onset schizophrenia and late-onset schizophreniform disorders. Current DSM-IV or ICD 10 nomenclatures do not differentiate between early- and late-onset schizophrenia. Many decades of repeated failures to provide for distinguishing neuropathological findings have prompted narrower definition criteria. Since psychotic or schizophreniform symptoms in old age may be a manifestation of Alzheimer's disease, we attempted to base a distinction between both early- and late-onset schizophrenia on the presence of degenerative changes. This study examined the brains of 64 schizophrenic patients and 18 controls immunocytochemically for tau and amyloid staining. We divided patients according to their ages at the onset of symptoms: <40, >40. Using Braak's classification, we assessed the presence of neurofibrillary pathology. Stages III and IV were observed in 11.1% (2/18) of controls, 36.7% (11/30) of early-onset schizophrenics (<40) and 58.8% (20/34) of late-onset (>40) schizophrenics (chi2=11.39, P =0.003). Stages V and VI (definite Alzheimer's disease) did not significantly differ among groups (chi2=3.6, P =0.165). Astrocytes, subependymal and fibroblastic, also exhibited tau-positive tangles. Chi-square analysis of the data revealed a significant association between tau-positive glial tangles and Braak staging ( P =0.002). Amyloid deposits were sparse in comparison to tau-related changes. The restricted limbic tauopathy not only affected a majority of patients with late-onset schizophrenia (19 female: 1 male among positive cases) ( P =0.048) but also appeared in one-third of those elderly schizophrenic patients whose symptom onset occurred before 40 years of age (8 female: 3 male among positive cases) ( P =0.048). The resultant changes define a type of neuronal cytoskeletal disruption that alters the flow of information through the hippocampus and provides a useful clinico-pathological correlate to a group of patients until recently diagnosed as schizophrenic.