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Study links progressive aphasia syndrome to prion gene

Most people with a rare type of dementia called primary progressive aphasia (PPA) have a specific combination of prion gene variants, a new study shows. The study is the first to link the prion protein gene to this disorder. It was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH), and appears in the December 2005 issue of the Annals of Neurology.[1]

The researchers, led by James A. Mastrianni, M.D., Ph.D., of the University of Chicago, also looked at the prion protein gene in people with Alzheimer's disease and amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) and did not find any association with specific gene variants in those disorders.

PPA is classified as a type of frontotemporal dementia because of the pattern of brain degeneration it causes. The primary symptoms of the disease are problems speaking or understanding speech, and these problems gradually get worse over time. People with PPA also may develop difficulty with math. Most other functions remain normal for at least two years after the language symptoms appear, but the disease may eventually cause other changes, such as problems with memory, reasoning, and spatial abilities. While PPA sometimes runs in families, it has never before been linked to variations in a specific gene.

Unlike the abnormal disease-causing prions linked to Creutzfeldt-Jakob disease (CJD) and other so-called "prion diseases", the normal prion protein is found in everyone. The gene that codes for the normal protein has several common variants. One variant of the gene codes for an amino acid called methionine at a point called codon 129, while another version codes for the amino acid valine at codon 129. These variants appear to influence disease susceptibility and symptoms in CJD and other prion diseases, probably because they determine how the prion protein folds. Proteins' folded s
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Contact: Natalie Frazin or Paul Girolami
301-496-5924
NIH/National Institute of Neurological Disorders and Stroke
28-Nov-2005


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