Alzheimer's disease is characterized by numerous abnormalities of metabolic pathways. A recent Chinese study (Xiao-hang Qian et al. 2023) investigated the relationship of the pathology with branched-chain amino acid (BCAA) metabolism disorders and found that Alzheimer's is associated with a decrease in the level of BCAAs, which therefore can serve as a marker for the early diagnosis of the pathology. (1)
Impact of Alzheimer's on public health
Alzheimer's disease (AD) is the leading type of dementia, and is becoming one of the most serious threats to public health worldwide. (2) It is estimated that there are more than 50 million people with dementia worldwide today, and will triple by 2050. (3) AD accounts for 60-80% of the various types of dementia.
Currently there is no accurate explanation of the pathogenesis and no effective therapeutic strategies are known.
The metabolism of branched-chain amino acids
The BCAAs they 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 muscle, brain, liver, and adipose tissue. The brain absorbs BCAAs into the blood to involve them in multiple functions, including neurotransmitter synthesis, protein synthesis, and energy production.
BCAA levels and Alzheimer's risk
Several studies have shown that impaired BCAA metabolism is associated with Alzheimer's. (4) Altered BCAA concentration in AD patients was thus associated with disease progression and related pathological features (5).
The results collected however they are controversial. This may be related to the susceptibility of the 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 study
was held in Shanghai, and consisted of a randomized two-way Mendelian study to evaluate the causal effect between BCAA levels (total BCAA, valine, leucine and isoleucine) and Alzheimer's risk.
The randomization Mendelian is a methodology that can be used to investigate the causal relationships between exposures (risk factors) and outcomes (diseases) using genetic variants. The genetic variants being related only to risk factors allow to obtain results not influenced by other susceptibility factors.
The results of the study they do not demonstrate that BCAA levels are causally related to Alzheimer's risk. Conversely, 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. For this reason, the variation of amino acid metabolism may serve as a marker for the early diagnosis of AD.
Emergedfurthermore, that supplementation of seven essential amino acids can improve cognitive, psychological and social functions in middle-aged and older adults. (7,8,9) Thus, BCAA supplementation may be one of the strategies to delay cognitive decline in Alzheimer's patients. Future studies will serve to investigate the mechanism that leads AD to reduce BCAA levels.
(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, MV 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, XX Song, XL Liu, et al. Tang. Inflammatory pathways in Alzheimer's disease mediated by gut microbiota. Aging Res Rev. (2021) 68:101317 . doi: 10.1016/j.arr.2021.101317
(5) J. Tynkkynen, V. Chouraki, SJ 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, WM 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 brain food. 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 for prevention and treatment. GIFT (Great Italian Food Trade) 2.4.22