Search for the Causes of Schizophrenia: Summary and Outlook

Journal of Abnormal Psychology, 86(2), 103-126

Alzheimer's disease is characterized by a widespread functional disturbance of the human brain. Fibrillar amyloid proteins are deposited inside neurons as neurofibrillary tangles and extracellularly as amyloid plaque cores and in blood vessels. The major protein subunit (A4) of the amyloid fibril of tangles, plaques and blood vessel deposits is an insoluble, highly aggregating small polypeptide of relative molecular mass 4,500. The same polypeptide is also deposited in the brains of aged individuals with trisomy 21 (Down's syndrome). We have argued previously that the A4 protein is of neuronal origin and is the cleavage product of a larger precursor protein. To identify this precursor, we have now isolated and sequenced an apparently full-length complementary DNA clone coding for the A4 polypeptide. The predicted precursor consists of 695 residues and contains features characteristic of glycosylated cell-surface receptors. This sequence, together with the localization of its gene on chromosome 21, suggests that the cerebral amyloid deposited in Alzheimer's disease and aged Down's syndrome is caused by aberrant catabolism of a cell-surface receptor.

In a group of schizophrenics of twin birth, no evidence of ventricular enlargement was found where there was a family history of major psychiatric disorder. Among those schizophrenics without such a family history, cerebral ventricular size was significantly increased (P less than 0.01), and there was also evidence of birth complications. Among normal control twins, those who reported complicated births had significantly larger ventricles.