STUDIES OF HUMAN DEVELOPMENT AND DEMENTIA WITH MONCLONAL ANTIBODIES

Abstract

Alzheimer's disease (AD) is a degenerative neurologic disorder whose etiology is unknown. Clinically the disease is marked by a progressive loss of intellectual function, while neuropathologically there is diffuse cortical atrophy especially in the temporal and frontal lobes of the brain. Characteristic microscopic lesions include neuritic plaques and neurofibrillary tangles.;From epidemiologic and pathologic studies, it is known that there is a link between AD and Down's syndrome (DS), a disease which results from triplication of band 21q22 of chromosome 21. Therefore, a somatic cell hybrid with 2.3 copies of chromosome 21 was used as an immunogen in mice in order to develop monoclonal antibodies to further characterize the protein products on chromosome 21, and investigate what relationship these might have to the etiology of AD. The panel of antibodies produced was studied using various immunologic and biochemical techniques, but efforts to characterize and identify the antigens were not successful.;Subsequent studies involved four antibodies from another available panel of monoclonals which had been prepared from mice immunized with ventral forebrain homogenates from AD patients. NP14 is an antibody which reacts with phosphorylated neurofilaments and ALZ-50 is a reagent which recognizes a protein with a molecular weight of 68,00 daltons. Brains of AD patients have been shown to contain 50 times as much of this antigen as normal age-matched controls. A developmental study of DS tissue using immunocytochemical techniques was performed with these two antibodies to further investigate the link between AD and DS. A second immunocytochemical study examined the presence of these two antigens in the brains of normal elderly patients in order to try to distinguish the changes of normal aging and AD pathology.;Two other antibodies from that series, NP6 and NP9, were found to react with chloroform methanol soluble antigens. Folch extraction and partition, and silicic acid chromatography, revealed that the antigens were glycolipids. Using purified lipid fractions in an enzyme-linked immunosorbent assay, the antibodies were shown to react with different galactolipids. These antibodies have been used to examine galactolipid composition of AD and Pick's disease brains.