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Alzheimer's Target Essential for Normal Myelination

Study shows reduced myelin sheath thickness in Bace1-knockout mice

WEDNESDAY, Nov. 15 (HealthDay News) -- The enzyme Bace1, a recently proposed therapeutic target for Alzheimer disease, is also essential for normal myelination in central and peripheral nerves, according to research reported Nov. 12 in an advance online publication of Nature Neuroscience. The results suggest Bace1 therapeutics may produce significant side effects.

Riqiang Yan, Ph.D., of the Cleveland Clinic in Ohio, and colleagues studied Bace1-knockout mice to determine its normal physiological role in axonal growth and brain development.

The investigators found that the process of myelination was delayed in the knockout mice and that their optic and sciatic nerves had reduced myelin thickness. The mice also showed impaired neurological function, including elevated pain sensitivity and reduced grip strength. Mechanistic studies showed a significant defect in the Akt signaling pathway that is important in myelin formation.

"It remains to be determined whether cleavage of neuregulin-1 is required for maintenance of the mature myelin sheath," the authors write. "If it is, inhibition of Bace1 activity as a targeted therapy for people with Alzheimer disease must be approached with caution."

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