Inhibition of beta-amyloid formation by haloperidol: a possible mechanism for reduced frequency of Alzheimer's disease pathology in schizophrenia.
Several reports have suggested that the frequency of Alzheimer's disease (AD) neuropathology is significantly reduced in elderly individuals with schizophrenia (SZ), and it has been proposed that medications used for treatment of SZ may be responsible. A central event in AD pathology is the formation of beta-amyloid (A beta) peptide, which is derived by enzymatic processing of its precursor protein. Haloperidol, an antipsychotic medication commonly used in the treatment of SZ, can act as an inhibitor of select proteinases; hence, we examined the ability of this compound to inhibit A beta formation by cultured cells. Haloperidol and, to a lesser extent, droperidol inhibited A beta in a dose-dependent manner. These results may explain the apparent reduction of AD neuropathological changes in elderly patients with SZ as well as provide a possible mechanism for this difference.
Higaki
J
J
Scios Inc., CA 94043, USA.
Murphy
G M
GM
Cordell
B
B
D000544:Alzheimer Disease / Q000150:complications* / Q000453:epidemiology*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D006220:Haloperidol / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015994:Incidence; D012559:Schizophrenia / Q000150:complications*
D016229:Amyloid beta-Peptides; D014150:Antipsychotic Agents; D006220:Haloperidol