Alzheimer’s disease is characterized by numerous abnormalities in metabolic pathways. A recent Chinese study (Xiao-hang Qian et al . 2023) investigated the relationship of the disease with disorders of branched-chain amino acid (BCAA) metabolism, finding that Alzheimer’s is associated with decreased BCAA levels, which thus may serve as a marker for early diagnosis of the disease. (1)
Impact of Alzheimer’s on public health
Alzheimer’s disease (AD) is the leading type of dementia, and it is becoming one of the most serious public health threats in the world. (2) It is estimated that there are currently more than 50 million people in the world with dementia, which will triple by 2050. (3) AD accounts for 60-80% of the various types of dementia.
Currently, an accurate explanation of the pathogenesis is lacking, and no effective therapeutic strategies are known.
The metabolism of branched-chain amino acids
BCAAs are essential amino acids and account for one-third of the total amino acid content of the human body. After being absorbed from the gut, BCAAs are widely distributed to many organs for metabolism, including the muscles, brain, liver, and adipose tissue. The brain absorbs BCAAs into the bloodstream to involve them in multiple functions, including neurotransmitter synthesis, protein synthesis, and energy production.
BCAA levels and the risk of Alzheimer’s disease.
Several studies have shown that altered metabolism of BCAAs is associated with Alzheimer’s disease. (4) The altered BCAA concentration in AD patients had thus been associated with disease progression and related pathological features (5).
However, the results collected are controversial. This may be related to the susceptibility of metabolites to multiple factors, such as lifestyle and diet, immune response, genetic variations, and gut microbiota (6), which make it difficult to distinguish symptoms from causes.
The Shanghai Mendelian randomized trial.
The research took place in Shanghai, and consisted of a two-way Mendelian randomized trial to evaluate the causal effect between BCAA levels (total BCAAs, valine, leucine, and isoleucine) and Alzheimer’s risk.
Mendelian randomization is a methodology that can be used to investigate causal relationships between exposures (risk factors) and outcomes (diseases) using genetic variants. Genetic variants being related only to risk factors allow for results that are not influenced by other susceptibility factors.
Results
The study results do not show that BCAA levels are causally related to Alzheimer’s risk. In contrast, the analysis suggests that AD is significantly associated with decreased BCAA levels, suggesting that the disease is the cause, not the result, of the change in BCAA levels. Therefore, variation in amino acid metabolism can serve as a marker for early diagnosis of AD.
It was also found that supplementation of seven essential amino acids can improve cognitive, psychological and social functions in middle-aged and older adults. (7,8,9) Therefore, BCAA supplementation may be one of the strategies to delay cognitive decline in patients with Alzheimer’s disease. Future studies will be needed to further investigate the mechanism that leads AD to reduce BCAA levels.
Giulia Pietrollini
Notes
(1) Q. Xiao-hang, L. Xiao-li, Z. et al. (2023). Investigating the causal association between branched-chain amino acids and Alzheimer’s disease: A bidirectional Mendelian randomized study. Front. Nutr.,Sec. Nutrition, Psychology and Brain Health, Vol. 10 – 2023 |10. 10.3389/fnut.2023.1103303. https://doi.org/10.3389/fnut.2023.1103303
(2) L. Xia , M. Quan , Y. Fu, et al. Dementia in China: epidemiology, clinical management, and research advances. Lancet Neurol. (2020) 19:81-92. doi: 10.1016/S1474-4422(19)30290-X
(3) MR. Irwin, M.V. Vitiello. Implications of sleep disturbance and inflammation for Alzheimer’s disease dementia. Lancet Neurol. (2019) 18:296-306. doi: 10.1016/S1474-4422(18)30450-2
(4) XH Qian, X.X. Song, X.L. Liu, et al. Tang. Inflammatory pathways in Alzheimer’s disease mediated by gut microbiota. Ageing Res Rev. (2021) 68:101317. doi: 10.1016/j.arr.2021.101317
(5) J. Tynkkynen, V. Chouraki, S.J. van der Lee, et al. Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer’s disease: A prospective study in eight cohorts. Alzheimer’s Demen. (2018) 14:723-33. doi: 10.1016/j.jalz.2018.01.003
(6) E. Horgusluoglu, R. Neff , W. M. Song, M. et al. Integrative metabolomics-genomics approach reveals key metabolic pathways and regulators of Alzheimer’s disease. Alzheimer’s Demen. (2022) 18:1260-78. doi: 10.1002/alz.12468
(7) Dario Dongo and Andrea Adelmo Della Penna. Omega 3, polyphenols and other food for thought. Scientific studies. GIFT (Great Italian Food Trade) 18.8.20
(8) H.Suzuki , D. Yamashiro , S. Ogawa, et al. Intake of seven essential amino acids improves cognitive function and psychological and social function in middle-aged and older adults: A double-blind, randomized, placebo-controlled trial. Front Nutr. (2020) 7:586166. doi: 10.3389/fnut.2020.586166
(9) Marta Strinati. Nutrition of the elderly to prevent and cure. GIFT (Great Italian Food Trade) 2.4.22
Graduated in industrial biotechnology and passionate about sustainable development.
