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AD/PD 2024 | BACE1 inhibitors: investigating the mechanisms of cognitive worsening

Robert Vassar, PhD, Feinberg School of Medicine, Northwestern University, Chicago, IL, discusses the value of investigating β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) inhibition in mice to further explore the mechanisms of cognitive worsening. The adverse effects on cognition observed in patients with Alzheimer’s disease (AD) after BACE1 inhibition were not neurodegenerative. Rather, adverse changes in cognition were rapid-onset, mild, and reversible. Accordingly, Dr Vassar emphasizes that research in mice is crucial to inform future clinical trials in patients with AD. Experimental BACE1 inhibition in mice may aid in identifying the substrate responsible for cognitive worsening. For efficacious therapeutic inhibition, drug dosage must be optimized to lower amyloid-β so that it confers benefit whilst remaining safe to use. This interview took place at the AD/PD™ 2024 congress in Lisbon, Portugal.

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