Alzheimer’s risk variant APOE4 linked to myelin-assembly malfunction

Carlström, Karl; Castelo-Branco, Gonçalo

doi:10.1038/d41586-022-03371-7

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16 November 2022

Alzheimer’s risk variant APOE4 linked to myelin-assembly malfunction

People who carry a particular variant of the APOE gene are at increased risk of developing Alzheimer’s disease. It emerges that this might be due to decreased production of a fatty substance called myelin by oligodendrocyte cells.

Karl Carlström⁰ &
Gonçalo Castelo-Branco¹

Karl Carlström
1. Karl Carlström is at the Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Biomedicum, 17177 Stockholm, Sweden.
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Gonçalo Castelo-Branco
1. Gonçalo Castelo-Branco is at the Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Biomedicum, 17177 Stockholm, Sweden, and at the Ming Wai Lau Centre for Reparative Medicine, Karolinska Institute.
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Oligodendrocytes are cells of the central nervous system that produce myelin — a lipid-rich, multilayered membrane that wraps around the cable-like extensions of nerve cells, allowing efficient insulation, rapid conduction of impulses and metabolic support. In diseases such as multiple sclerosis, a temporary or permanent loss of myelin translates into bouts of illness. But the changes seen in oligodendrocytes and their precursors in both multiple sclerosis¹ and Alzheimer’s disease²^–⁸ suggest that these cells might also contribute directly to the onset or progression of disease. Writing in Nature, Blanchard et al.⁹ unveil a previously unknown role for oligodendrocytes in Alzheimer’s disease that involves the lipid carrier protein apolipoprotein E (APOE) and changes in cholesterol metabolism.

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Nature 611, 670-671 (2022)

doi: https://doi.org/10.1038/d41586-022-03371-7

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