New therapies for Alzheimer’s disease are sorely needed, and some studies have hinted that molecules called phospholipids may bolster cognition and brain health. Whey protein powder, which is enriched in phospholipids, consist of a complex mixture of milk fat globule membrane (MFGM), whey protein, and casein derived from bovine milk. According to a recent study, MFGM may be the component of whey protein powder that helps alleviate cognitive and physiological pathology in a mouse model of the Alzheimer’s disease (1).
Phospholipids are present in high concentrations in the brain. Researchers have found a decrease of certain phospholipids in older adults experiencing cognitive decline (2). Enriching phospholipids in the diet of mice improves short-term learning and memory (3). What’s more, MFGM in particular has been shown to increase the expression of genes involved in brain function in rats (4) and possibly to contribute to cognitive performance in human infants (5).
To determine whether MFGM may ameliorate aspects of Alzheimer’s disease, researchers in China tested its effect on a mouse model in which the animals were engineered to have three mutations associated with genetic forms of the disease. These mice develop the hallmark physiological symptoms of Alzheimer’s, including amyloid beta plaque deposits, neurofibrillary tangles caused by the accumulation of a protein called tau, and brain inflammation. They also have learning and memory deficits as measured by their performance on maze tests.
Through pathological and multiomics analysis, the researchers elucidated the effect of whey protein powder with MFGM in ameliorating inflammation and improving cognitive function of AD mice. They examined the effects of whey protein powder by studying the brains and behavior of control mice (without the mutations) that ate regular chow, mice with the mutations that ate regular chow, and mice with the mutation that were fed the protein powder in addition to chow. After three months of ingesting whey protein powder, the Alzheimer’s disease model mice showed stronger performance in water maze tests—and thus improved cognitive performance—as well as on a test for anxiety, compared with Alzheimer’s disease mice that did not consume whey protein powder. Mice that consumed whey protein powder also had lower levels of amyloid beta molecules their brains and lower levels of tau protein.
Additionally, the researchers pinpointed how the dietary whey protein powder may have exerted its brain-protecting effect. In studies on homogenized cortical tissue, they identified dozens of genes that were differentially expressed in the control mice, the Alzheimer’s disease mice, and the Alzheimer’s disease mice that consumed whey protein powder. These differences in expression were especially strong in genes associated with inflammatory signaling pathways. They also identified several metabolites in cortical tissue that were present in different amounts among the three groups. Most of these belonged to a group of lipid or lipid-like molecules and many enriched the fatty acid metabolism pathway.
One metabolic pathway in particular, called the PPAR signaling pathway, which acts as a lipid sensor and regulates lipid metabolism, was implicated in these differences. In further studies the researchers found a regulatory effect of whey protein powder on the PPAR pathway, which in turn affected a related signaling pathway called mTOR. mTor has been linked to inflammatory factors in the brains of people with Alzheimer’s disease (6).
Overall, the study suggests that dietary whey protein powder merits further inquiry for treating at least some aspects of neurodegenerative disease. “Our results provide new insights into the underlying mechanism of [whey protein powder] and more evidence for its efficacy in alleviating” Alzheimer’s disease, the authors write in the study (1). — By Alla Katsnelson, Ph.D, International Milk Genomics Consortium
- Li Y, Zhang ZH, Huang SL, Yue ZB, Yin XS, Feng ZQ, Zhang XG, Song GL. Whey Protein Powder with Milk Fat Globule Membrane Attenuates Alzheimer’s Disease Pathology in 3×Tg-AD Mice by Modulating Neuroinflammation Through the Peroxisome Proliferator-activated Receptor γ Signaling Pathway. J Dairy Sci. 2023: 106(8):5253-5265.
- Liu TT, Pang SJ, Jia SS, Man QQ, Li YQ, Song S, Zhang J. Association of Plasma Phospholipids with Age-Related Cognitive Impairment: Results from a Cross-Sectional Study. Nutrients. 2021:13(7):2185.
- Schipper L, van Dijk G, Broersen LM, Loos M, Bartke N, Scheurink AJ, van der Beek EM. A Postnatal Diet Containing Phospholipids, Processed to Yield Large, Phospholipid-Coated Lipid Droplets, Affects Specific Cognitive Behaviors in Healthy Male Mice. J Nutr.2016:146(6):1155-1161.
- Brink LR, Lönnerdal B. The Role of Milk Fat Globule Membranes in Behavior and Cognitive Function Using a Suckling Rat Pup Supplementation Model. J Nutr Biochem. 2018:58:131-137. (Preprint)
- Hernell O, Timby N, Domellöf M, Lönnerdal B. Clinical Benefits of Milk Fat Globule Membranes for Infants and Children. J Pediatr. 2016:173 Suppl:S60-5.
- Thakur S, Dhapola R, Sarma P, Medhi B, Reddy DH. Neuroinflammation in Alzheimer’s Disease: Current Progress in Molecular Signaling and Therapeutics. Inflammation. 2023:46(1):1-17.