Amyloid β Pathology in Alzheimer’s Disease and Schizophrenia

OBJECTIVE: Severe cognitive impairment is common in elderly patients with schizophrenia. Alzheimer’s disease is the main cause of dementia among the elderly. Biochemical and genetic studies suggest that amyloid β-peptide is central in Alzheimer’s disease. The authors examined the possible involvement of amyloid β-peptide in cognitive impairment in schizophrenia. METHOD: Specific antibodies against two major forms of amyloid β-peptide, Aβx-40 and Aβx-42, were used in sandwich enzyme-linked immunosorbent assays to determine the levels of amyloid β-peptide in postmortem brain samples from Alzheimer’s disease patients (N=10), normal elderly comparison subjects (N=11), and schizophrenia patients with (N=7) or without (N=26) Alzheimer’s disease. RESULTS: The levels of amyloid β-peptide were highest in the Alzheimer’s disease patients, followed by the patients with schizophrenia and comparison subjects. The mean Aβx-42 level in the schizophrenia patients without Alzheimer’s disease was similar to that in the comparison subjects, but the level in the schizophrenia patients with Alzheimer’s disease was significantly higher than in those without Alzheimer’s disease or the comparison subjects. The Aβx-42 level in the schizophrenia patients with Alzheimer’s disease was significantly lower than the level in the Alzheimer’s disease cohort. CONCLUSIONS: In contrast to elderly schizophrenia patients with Alzheimer’s disease pathology, those without Alzheimer’s disease had amyloid β-peptide levels that were not significantly different from those of normal subjects; hence amyloid β-peptide does not account for the cognitive deficits in this group. These results suggest that the causes of cognitive impairment in “pure” schizophrenia are different from those in Alzheimer’s disease.