Credit: Max-Delbrück-Center, Berlin

An enzyme that helps generate clumps of amyloid-β in the brains of people with Alzheimer disease also has a role in myelinating axons, according to a study in Science (doi: 10.1126/science.1132341). The findings sound a cautionary note for ongoing efforts to develop drugs to inactivate this enzyme.

The enzyme, BACE1 (beta-site amyloid precursor protein–cleaving enzyme 1), is required to cleave amyloid-β from a larger precursor. (After BACE1-mediated cleavage, the presenilin-containing complex γ-secretase makes the final cleavage, liberating amyloid-β.)

Michael Willem et al. found that BACE1 seems to be required for processing a signal, the EGF-like factor neuregulin 1,that activates receptors on Schwann cells. Activation of these receptors is required for myelination.

One observation supporting this hypothesis was that animals deficient in BACE-1 had myelin defects in the peripheral nerves. Shown is a cross-section of the sciatic nerve of an 8-day-old BACE1-deficient mouse; myelin sheath in black. The myelin is thinner than in wild-type mice and some axons lack myelin altogether.

Peripheral nerve myelination occurs early in life, so it is unclear how BACE1 inhibition might affect older animals. Whether BACE1 also has a role in myelination of the central nervous system is also unclear.