Cognitive impairment is prevalent in older schizophrenia patients but its biological basis is unknown. Neuropathological studies have not revealed Alzheimer disease (AD) lesion burden but in vivo data are lacking.We investigated the concentrations of CSF biomarkers of brain amyloidosis (Abeta42) and neurodegeneration (total and p-tau) in a group of older schizophrenia patients and related them to cognitive and MRI measures. Older schizophrenia (n = 11), AD patients (n = 20) and elderly controls (n = 6) underwent cognitive testing, lumbar puncture, and MRI scanning. Abeta42 and total and p-tau concentrations were assayed in the CSF. MRI volumes were assessed using both voxel-based (cortical pattern matching) and region-of-interest analyses.CSF tau concentration in older schizophrenia patients was within normal limits (total tau 171 ± 51 pg/ml, p-tau 32 ± 8 pg/ml), while CSF Abeta42 (465 ± 112 pg/ml) levels were significantly lower compared to healthy elders (638 ± 130 pg/ml) but higher than in AD patients (352 ± 76 pg/ml). There was a strong positive relationship between CSF total or p-tau levels and MMSE scores in schizophrenia patients but not in AD, where higher concentrations of total tau were correlated with higher volumes in the occipital cortex (r = 0.63, p = 0.036), while in AD a significant correlation was found between lower Abeta42 concentrations and lower gray matter volume in the cingulate and lateral orbital cortices (r > 0.46, p < 0.05).Older schizophrenia patients show a peculiar pattern of CSF Abeta42 and tau concentrations that relates to cognitive and structural markers but is not consistent with neurodegeneration and could be secondary to neurodevelopmental or drug treatment effects.