Prospect of Muscle-Building Supplement HMB in Alzheimer's Disease

Alzheimer's disease (AD) is the most common progressive and irreversible neurodegenerative disorder in humans that affects memory, thinking and behavior. Impairment in synaptic plasticity is one of the hallmarks in AD, with most of the impairment occurring in the hippocampal region, a key part of the brain for memory and learning. Therefore, the upregulation of hippocampal plasticity is critical to remediate the progression of AD and preserve memory formation and cognitive functions. Recent studies have described β-hydroxy-β-methylbutyrate (HMB), a body building supplement commonly used by athletes, as a candidate molecule for improving hippocampal plasticity. Clinically, AD is characterized by the abnormal accumulation of beta amyloid (Aβ) plaques, coupled with intracellular aggregates of hyperphosphorylated tau protein. In addition to enhancing hippocampal plasticity, HMB has been also demonstrated to lower amyloid plaques in a mouse model of AD. Although liver is rich in peroxisome proliferator-activated receptor alpha (PPARα), recent findings have established the presence of PPARα in hippocampus and other parts of the brain. Interestingly, HMB has been shown to utilize PPARα for lowering plaques and increasing hippocampal plasticity. Here, we discuss these newly described features of HMB with possible implications for the use of HMB supplement in patients with dementia and AD.