Molecular misreading of genes in Down syndrome as a model for the Alzheimer type of neurodegeneration

The occurrence of +1 frameshifted proteins, such as amyloid precursor prote in (APP(+1)) and ubiquitin-B (UBB+1) in Down syndrome (DS) has been linked to the onset of Alzheimer's disease (AD). In DS and AD patients, but also i n elderly non-demented persons, these co-called +1 proteins accumulate in t he neuropathological hallmarks (neurofibrillary tangles, dystrophic neurite s of the neuritic plaques and neuropil threads) and may have deleterious ef fects on neuronal function. Frameshifts are caused by dinucleotide deletion s in GAGAG motifs in messenger RNA and are now thought to be the result of unfaithful transcription of normal DNA by a novel process termed "molecular misreading". In the present review some of the critical events in molecula r misreading are discussed, the emphasis being on DS.