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Review
. 2025 Feb 12.
doi: 10.1113/JP288032. Online ahead of print.

The link between sarcopenic obesity and Alzheimer's disease: a brain-derived neurotrophic factor point of view

Emily N Copeland  1   2 , Paul J LeBlanc  2   3 , Paula Duarte-Guterman  4   5 , Val A Fajardo  1   3 , Rebecca E K MacPherson  2   5
Affiliations
Review

The link between sarcopenic obesity and Alzheimer's disease: a brain-derived neurotrophic factor point of view

Emily N Copeland et al. J Physiol. .

Abstract

Age-related diseases are becoming more prominent as the lifespan of the global population rises. Many of these diseases coincide with each other and can even influence the onset of additional comorbidities. Sarcopenic obesity is described as age-related loss of muscle mass that concurs with excessive weight gain and tends to increase the risk of comorbidity development, including Alzheimer's disease (AD). Though the exact link between sarcopenic obesity and AD is not known, this review explores the possibility that reduced levels of brain-derived neurotrophic factor (BDNF) throughout the body may serve as the underlying commonality. In AD, reductions in BDNF signalling through its receptor promote the activation of glycogen synthase kinase 3 beta (GSK3β), which subsequently increases the production of amyloid beta (Aβ) peptides and neurofibrillary tangles (NFTs). In the skeletal muscle, lower BDNF concentrations are linked to impaired muscle fibre repair and regeneration, increasing the likelihood of sarcopenia. Furthermore, the absence of BDNF impairs mitochondrial function, leading to insulin resistance and increased adiposity. BDNF concentration has a negative relationship with obesogenic markers in adipose tissue, and as such, lower concentrations of BDNF lead to weight gain. Collectively, current literature suggests that BDNF attenuates AD pathology while improving skeletal muscle mitochondrial function, whole-body insulin resistance and facilitating adipocyte browning. Therefore, BDNF may be a viable target for multiple age-related diseases, but more research is required to substantiate this claim, with a particular focus on examining any potential influence of biological sex, as women are at a higher risk for both AD and sarcopenic obesity.

Keywords: adipose tissue; ageing; brain; crosstalk; skeletal muscle.

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