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Alzheimer disease: presenilin springs a leak

Nature Medicine volume 12, pages 1121–1123 (2006)Cite this article

Presenilins are thought to contribute to Alzheimer disease through a protein cleavage reaction that produces neurotoxic amyloid-β peptides. A new function for presenilins now comes to light—controlling the leakage of calcium out of the endoplasmic reticulum. Is this a serious challenge to the 'amyloid hypothesis' of Alzheimer disease?

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Figure 1: Calcium, amyloid-β, presenilin and Alzheimer disease.

Kim Caesar

Figure 2: Potential steps leading from familial Alzheimer mutations (APP mutations, PS1 mutations) to neurotoxicity and neurodegeneration, via either Aβ-dependent (left) or Aβ-independent (right) pathways.

Kim Caesar

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Authors and Affiliations

  1. Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, 19107, Pennsylvania, USA

    Sam Gandy

  2. Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, 19107, Pennsylvania, USA

    Mark K Doeven

  3. Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, AG Groningen, 9747, The Netherlands

    Mark K Doeven

  4. Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, AG Groningen, 9747, The Netherlands

    Bert Poolman

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  1. Sam Gandy
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  2. Mark K Doeven
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  3. Bert Poolman
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Gandy, S., Doeven, M. & Poolman, B. Alzheimer disease: presenilin springs a leak. Nat Med 12, 1121–1123 (2006). https://doi.org/10.1038/nm1006-1121

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