Beta amyloid peptide from diseased neurons can form pathological protein deposits and cause neurodegeneration in nearby normal tissue, reports a study in the April issue of Nature Neuroscience. The results suggest that amyloid outside cells, rather than within neurons, may be the type that is detrimental in Alzheimer's disease.
An international group of authors from Switzerland, Belgium and the US used transgenic mice that express a mutated version of the Alzheimer's precursor protein (the source of beta amyloid) to study the formation of abnormal protein deposits called ‘plaques’, which are a symptom of Alzheimer’s disease. They found plaques within grafts of normal tissue placed into the brains of mutant mice, suggesting that amyloid from outside the graft was able to diffuse in and form plaques. These normal tissue grafts also showed other signs of amyloid pathology and neurodegeneration. In contrast, when neuronal tissue from mutant mice was grafted into the brains of normal mice, no plaques were formed.
These results address a long-debated question of whether the amyloid is problematic when it is first produced within neurons or whether extracellular accumulation into plaques is the first step toward pathology. Although intracellular effects cannot be ruled out, it is clear from these results that extracellular amyloid is sufficient to induce plaque formation and other amyloid-associated pathologies.
Department of Neuropathology
University of Basel, Switzerland
Tel: +41 61 265 28 94
Additional contact for comment on paper:
David R. Borchelt
Department of Pathology
Johns Hopkins University School of Medicine
Tel: +1 410 502 5174
Also published online.
(C) Nature Neuroscience press release.
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