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Amyloid beta pathology in Alzheimer's disease and schizophrenia

, : Amyloid beta pathology in Alzheimer's disease and schizophrenia. American Journal of Psychiatry 160(5): 867-872

Severe cognitive impairment is common among elderly schizophrenics. Alzheimer's disease (AD) is the main cause of dementia in the elderly. Biochemical and genetic studies implicate a central role for amyloid beta-peptide (Abeta) in AD. The involvement of Abeta in cognitive impairment in schizophrenia was studied. Antibodies against Abetax-40 and Abetax-42 were used in sandwich ELISA assays to determine the levels of Abeta in postmortem brain from AD patients (N=10), controls (N=11) and schizophrenics with (N=7) or without AD (N=26). ANOVA followed by Newman-Keuls tests showed that the levels of Abeta were highest in AD cases (p=0.003), followed by schizophrenics and controls. Levels of Abetax-42 were similar in demented schizophrenics without AD and controls, but they were significantly higher in schizophrenics with AD vs. controls or vs. schizophrenics without AD (ps<0.007). The levels of Abetax-42 in schizophrenics with AD neuropathology was significantly lower than its levels in the AD cohort (p=0.0001). In contrast to elderly schizophrenics with AD pathology, Abeta levels in demented schizophrenics without AD were not significantly different from controls, hence Abeta does not account for the cognitive deficits in schizophrenia. These results suggest that the causes of cognitive impairment in "pure" schizophrenics are different than those in AD. Thus, although schizophrenics with AD could benefit from Abeta-targeting therapeutics, most other elderly schizophrenics will likely be refractory to such interventions.


PMID: 12727689

DOI: 10.1176/appi.ajp.160.5.867

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