FRAMESHIT MUTANTS OF BETA-AMYLOID PRECURSOR PROTEIN AND UBIQUITIN-B IN ALZHEIMERS AND DOWN PATIENTS

The cerebral cortex of Alzheimer's and Down syndrome patients is chara cterized by the presence of protein deposits in neurofibrillary tangle s, neuritic plaques, and neuropil threads. These structures were shown to contain forms of beta amyloid precursor protein and ubiquitin-B th at are aberrant(+1 proteins) in the carboxyl terminus. The +1 proteins were not found in young control patients, whereas the presence of ubi quitin-B+1 in elderly control patients may indicate early stages of ne urodegeneration. The two species of +1 proteins displayed cellular col ocalization, suggesting a common origin, operating at the transcriptio nal level or by posttranscriptional editing of RNA. This type of trans cript mutation is likely an important factor in the widely occurring n onfamilial early- and late-onset forms of Alzheimer's disease.