Serum IgG brain reactive antibodies in Alzheimer disease and Down syndrome

The cause(s) of Alzheimer disease (AD) remain unknown. Since neurofibrillary tangles and neuritic plaques, a hallmark of AD, are also present in older patients with Down syndrome (DS), a close relationship between the two diseases has been suggested. IgG type of brain reactive antibodies (BRAs) are present in a majority of patients with AD but such studies have not been carried out in adult patients with DS. The present study was carried out to test the hypothesis that if the brain changes in older patients with DS and patients with AD are identical, the occurrence and specificity of BRAs should be similar in both diseases. The frequency of BRAs was studied in sera obtained from 21 patients with AD, 26 older patients with DS, and 20 normal control subjects using electroblots prepared from rat spinal cord proteins. Circulating BRAs were found in 57% of patients with AD, 81% of patients with DS, and 30% of normal controls. However, the pattern of BRA reactivity was different in AD and DS. In AD, antibodies reacted with the 200-kDa subunit of neurofilament triplet singly or in combination with the 150-kDa, 70-kDa or with the associated 62-kDa protein. In DS, BRAs always reacted with the 70-kDa protein, usually in combination with the 200-kDa subunit and, less frequently, in association with the other subunits. No specific pattern of antibody activity was evident in the control group.