- Prior research suggests that physical activity can slow down the development of Alzheimer’s disease and the accompanying abnormal accumulation of beta-amyloid and tau protein in the brain.
- A new study involving aged rats suggests that exercise may influence the interactions between brain cells in the hippocampus, a brain region involved in learning and memory.
- These findings could help illuminate potential mechanisms underlying the protective effects of exercise against aging and Alzheimer’s disease.
The number of individuals living with dementia was 57 million in 2019, and is expected to grow almost threefold, to 153 million, by 2050. The rapid rise in cases, which are mainly due to Alzheimer’s disease, and the lack of a cure highlights the importance of preventative measures such as physical exercise.
A recent study in old rats published in Brain Research suggests that exercise may modulate the interaction between brain cells to improve their survival and reduce inflammation and the abnormal accumulation of proteins associated with aging and Alzheimer’s disease.
Study author Augusto Coppi, PhD, senior lecturer at the University of Bristol in the United Kingdom, said in a press release: “While physical exercise is known to reduce cognitive decline, the cellular mechanisms behind its neuroprotective effects have remained elusive — until now. This research highlights the potential for aerobic exercise to serve as a cornerstone in preventive strategies for Alzheimer’s disease.”
Ryan Glatt, MS, CPT, NBC-HWC, brain health coach and director of the FitBrain Program at Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA, who was not involved in this research, told Medical News Today:
”The study provides valuable insight into how exercise might mitigate Alzheimer’s pathology by reducing brain inflammation, iron overload, and improving cellular communication in the hippocampus. While these findings are compelling, they are based on animal models, and the exact mechanisms need validation in human trials.”
Studies have shown that exercise is associated with a reduced risk of developing Alzheimer’s disease. Moreover, animal studies have shown that exercise helps prevent the abnormal accumulation of tau and beta-amyloid protein in the brain, which are key factors in the development of Alzheimer’s.
The beta-amyloid protein forms insoluble aggregates called amyloid plaques in the space between brain cells. In contrast, the tau protein aggregates to form insoluble fibrils, referred to as neurofibrillary tangles, inside the cells.
The tau protein is a critical part of the cell skeleton, known as the cytoskeleton, and the deposits of insoluble tau disrupt the structure of brain cells. These plaques and tangles are thought to be the main biological features of Alzheimer’s disease.
However, the absence of symptoms of Alzheimer’s disease in some individuals with beta-amyloid and tau deposits in their brains has led to alternative hypotheses.
For instance, the degeneration of the myelin sheath, the fatty membrane that envelops and insulates nerve cells that carry electrical impulses, has been hypothesized to promote the abnormal accumulation of proteins in the brain and the development of Alzheimer’s disease.
The myelin sheath is generated by oligodendrocytes, a type of nerve cell. The process requires iron but excessive accumulation of iron can result in oxidative stress and death of oligodendrocytes.
Studies have also shown the accumulation of iron deposits during aging and Alzheimer’s disease in brain regions that coincide with those showing the formation of beta-amyloid and tau protein aggregates.
Previous studies in rodents have shown a positive impact of exercise on brain health and cognition. These studies have demonstrated that exercise can have a protective effect on the hippocampus, a brain region involved in learning and memory.
Specifically, exercise promotes the generation and survival of brain cells while protecting the connections between them.
Moreover, it is associated with slowing down the accumulation of beta-amyloid and tau aggregates and reducing brain inflammation and oxidative stress that are associated with aging and Alzheimer’s disease.
In the present study, the researchers further examined the impact of exercise in protecting the different types of brain cells in the hippocampus of aged rats. In addition, they also assessed the impact of exercise on the accumulation of beta-amyloid and tau aggregates and iron in the hippocampus and how these deposits influenced the various brain cells.
The researchers did not use genetically modified rodent models of Alzheimer’s disease because they do not recapitulate all features of the condition observed in humans. These features include the cooperation between the beta-amyloid and tau proteins.
Instead, they used aged rats because they show a similar accumulation of protein aggregates and iron in the brain to that observed in Alzheimer’s disease.
The study involved 10 animals, five in the experimental group that engaged in regular physical activity and five in the control group that did not engage in physical exercise. The training regimen for the physical activity group involved exercise on a treadmill for five sessions per week lasting up to 30 minutes over an 8-week period.
The researchers euthanized the animals after this 8-week period, and stained their brains to quantify the different cell types in the hippocampus and detect the levels of beta-amyloid, tau, and iron accumulation.
The researchers found that the hippocampus of the rats in the physical exercise group showed twice as many pyramidal and granule nerve cells as the control group.
The volumes occupied by the tau and beta-amyloid aggregates were also smaller in the hippocampus of aged rats in the physical exercise group. In addition, the exercise group showed a higher number of normal oligodendrocytes but a lower number of oligodendrocytes with iron deposits.
The researchers observed several correlations among the cell types and iron/protein deposits, with exercise positively affecting some of the correlations. These correlations, with cell types and deposits being mutually affected, indicate possible cross-talk between cell types.
For example, exercise may help prevent the accumulation of iron in oligodendrocytes, which may, in turn, help protect other nerve cells.
The number of oligodendrocytes with iron deposits was associated with the volume of the neurofibrillary tau aggregates, both increasing in the sedentary rats and decreasing in the active rats. The researchers say their findings “may indicate that iron overload in the oligodendrocytes […] could be a pathological sign in Alzheimer’s disease brains”.
The rats in the exercise group also showed fewer activated microglia, a type of immune cells, in the hippocampus. Dysfunction of microglial cells is typically observed in old age, and exercise may help reduce the activation of microglia and, thus, aging-related inflammation.
While these results suggest that exercise influences the cross-talk between brain cells to counter the effects of aging, Glatt noted, “future trials are needed to confirm these mechanisms and determine optimal exercise types and doses for targeted neuroprotection.“
“While exercise is undoubtedly beneficial, claims about specific molecular pathways should be approached cautiously until more robust human data is available,” he advised.
