Physical activity and prevention of Alzheimer's disease.

Alzheimer's disease (AD) is an irreversible, progressive brain disorder that affects about 48 million people worldwide and is the cause of 60%–70% of dementia, particularly in people over 65 years old. Without prevention or treatment, the disease slowly destroys memory and thinking skills and, eventually, the individual loses the ability to carry out the simplest tasks. Unfortunately, there is no drug available to stop or reverse the progress of AD so far. Although 70% of the risk of AD is believed to be genetic, recent studies found that environmental and lifestyle factors may play a role in the development and course of AD and that physical activity might help to reduce the risk of cognitive decline of AD. In this special section, we invited 5 world-recognized clinical and basic scientists who specialize in AD studies to present the most recent discoveries: biomarkers for AD (Hampel et al.), the newest drug development (Vassar), potential anti-Tau therapy (Takashima), microbiome as a novel therapeutic approach (Lukiw), and exercise in the prevention of AD (Shen and Li).

AD does not occur in 1 day; it develops slowly from mild to moderate to severe over many years. Indeed, the initial symptoms of AD are often confused with normal aging, such as wandering, getting lost, repeating questions, and taking longer to complete normal daily tasks, as well as personality and behavior changes. Identifying the early stage of AD and developing prevention tools to stop or slow the progress of the disease are critical. The biomarkers for AD diagnosis at an early stage will provide objective and reliable measures of disease progress. Dr. Hampel is an internationally recognized leader in the discovery of biomarkers for AD. In his manuscript entitled “Biomarker-guided classification scheme of neurodegenerative diseases”, he and his colleagues presented an unbiased descriptive classification system for neurodegenerative dementia, including AD, and clinical and biomarker information. Such important information would allow the characterization and identification of AD even at the earliest asymptomatic preclinical stage through population-based screening.

Although there is no drug that can stop or prevent AD, there are several therapeutic candidates that have been actively developed over the past few years, including inhibitor of beta secretase (BACE). BACE is a key enzyme for cleaving amyloid precursor protein, a major protein associated with AD. Blocking BACE in animal models showed a great effect in reducing AD pathologic changes. Dr. Vassar is one of the 4 scientist groups who first discovered BACE in 1999, when his discovery was published in Science; the other 3 groups published in Nature7, 8 and Molecular and Cellular Neuroscience at the same time. Since then, Dr. Vassar has been working on BACE as the best and most possible drug for AD. In his article entitled “BACE1 inhibition as a therapeutic strategy for Alzheimer disease” we learn the most current information on drug discovery using BACE inhibitors from animal to clinical trials.

Another major pathologic feature of AD is Tau protein, which forms special twisted strands as tangles and destroys neurons in the brain. Understanding how Tau protein causes AD and developing anti-Tau therapy have been the major focus of Dr. Takashima's research. In his paper entitled “Mechanism of neurodegeneration through Tau and therapy for Alzheimer's disease”, he explains his studies on Tau in AD and offers novel insights about Tau aggregation pathology, particularly suggesting that inhibition of Tau aggregation might be a promising option for blocking AD progression.

“From gut to brain” is a new discovery and a novel approach for AD research. Increasing evidence indicates that the human microbiome may contribute to the regulation of the communication between the gastrointestinal (GI) tract and the central nervous system. Studies of AD demonstrated that dysregulation of microbiomes in the GI tract could be associated with the progression of AD and that “good gut bacteria” may delay AD-associated cognitive impairment. Dr. Lukiw was one of the scientists who first reported the microbial-neuronal interaction in AD. In his short article entitled “The microbiome, microbial-generated proinflammatory neurotoxins, and Alzheimer's disease”, we learn about the most recent publications on the potential contribution of microbiome-generated factors in proinflammatory signaling in the brain as well as the recent recognition of the beneficial effects of dietary fibers on the human GI tract microbiome, with specific reference to AD neuropathology.

Finally, we would like to know whether exercise can prevent, stop, or reverse AD. During the past decades, extensive studies have demonstrated that exercise is good and important for people with AD, particularly for reducing some of the AD symptoms. In general, exercise may help elderly people to sleep, lower their anxiety level, and prevent falls. Interestingly, recent studies found that exercise or regular physical activity might also play a role in AD. Dr. Shen is a world-recognized AD research scientist who presented the most recent findings on exercise and AD. In his article entitled “What do we know from clinical trials on exercise and Alzheimer's disease?” he gathered the findings from the most current clinical trials on exercise in AD and focused on the effects of physical exercise, cognitive stimulation, and a combination of both physical and cognitive training on protection and rescue from cognitive decline in people with AD.

Together, we are very lucky and excited to have a group of outstanding scientists from around the world to share their most recent discoveries or visions on AD research and the potential of exercise intervention in prevention and treatment of this disease. We hope that this special section of the Journal of Sport and Health Science will not only provide our readers with a view of AD but also open a new window to search for future approaches to using exercise to stop and treat the disease.