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Alzheimer's disease

A protective mutation

Nature volume 488, pages 38–39 (2012)Cite this article

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A rare gene variant has been found that decreases the peptide deposition seen in the brains of people with Alzheimer's disease. The mutation may also slow the normal cognitive decline that occurs with age. See Letter p.96

Although our understanding of the biological processes causing Alzheimer's disease remains hazy, one clear defining feature of the disease is an accumulation in the brain of deposits of amyloid-β peptides. These form following cleavage of the amyloid precursor protein (APP), and mutations in the APP gene can affect this cleavage and/or the biophysical properties of the peptides1, leading to their aggregation into toxic peptide assemblies2,3 that propagate in the brain and promote neurodegeneration4,5. All APP mutations identified so far increase levels of these toxic amyloid-β species, but might APP mutations exist that act in the opposite way, by reducing peptide accumulation and protecting against neurodegeneration? On page 96 of this issue, Jonsson et al.6 report finding the proverbial needle in a haystack: a rare variant of the APP gene that protects against Alzheimer's disease.

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Figure 1: Amyloid precursor protein and Alzheimer's disease.

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Authors and Affiliations

  1. Bart De Strooper and Thierry Voet are in the Center for Human Genetics and Leuven Research Institute for Neurodegenerative Disorders, KU Leuven, 3000 Leuven, Belgium.,

    Bart De Strooper & Thierry Voet

  2. B.D.S. is also at the VIB Center for the Biology of Disease, Leuven.,

    Bart De Strooper

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  1. Bart De Strooper
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  2. Thierry Voet
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Correspondence to Bart De Strooper.

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Competing interests

B.D.S. is a consultant for Janssen Pharmaceutica, Beerse; Envivo Pharmaceuticals, Boston; and Remynd NV, Leuven. He also receives research funding from Janssen Pharmaceutica, Beerse.

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De Strooper, B., Voet, T. A protective mutation. Nature 488, 38–39 (2012). https://doi.org/10.1038/488038a

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