Exercise really does help prevent dementia — and this protein is why

A protein secreted by muscles during exercise may offer a new clue to the earliest changes in Alzheimer's disease, according to a South Korean study. The researchers said they confirmed the possibility of using blood levels of a specific protein to screen for Alzheimer's risk at an early stage, and expressed hope that the findings could inform the development of blood-based dementia diagnostics and prevention strategies.

A research team led by Kang Sung-hoon, a professor of neurology at Korea University Guro Hospital, confirmed that irisin — a protein released by muscles during exercise — is closely linked to amyloid accumulation in the brain, the hallmark pathology of Alzheimer's disease. The team included Jeong Young-hee of Hallym University Pyeongchon Sacred Heart Hospital's neurology department, Lee Eun-seong of Korea University Guro Hospital's nuclear medicine department, and Kim Hyun-su of Korea University College of Medicine's anatomy department.

The earliest known pathological change in Alzheimer's disease is the buildup of amyloid protein in the brain. As nerve cell damage progresses, the condition leads to memory decline, cognitive impairment and ultimately dementia.

Earlier animal studies had reported that irisin could promote the clearance of amyloid from the brain, but few studies had analyzed blood irisin levels alongside the degree of brain amyloid accumulation in human subjects.

The research team conducted blood tests, amyloid positron emission tomography (PET) scans and neuropsychological assessments on 100 elderly participants spanning the preclinical stage of Alzheimer's disease through the dementia stage.

Participants were divided into four groups — an amyloid-negative cognitively normal group, an amyloid-positive asymptomatic group, an amyloid-positive mild cognitive impairment group, and an Alzheimer's disease dementia group — and the team comprehensively analyzed the relationships among blood irisin levels, degree of brain amyloid accumulation and cognitive function.

All three groups with brain amyloid accumulation showed lower blood irisin levels than the normal group. Particularly notable was a significant reduction in irisin levels even at the asymptomatic stage — when amyloid had already accumulated but cognitive decline had not yet appeared — suggesting the protein may reflect biological changes before symptoms emerge.

The analysis also found that higher blood irisin levels corresponded to lower Centiloid scores, the measure used to quantify brain amyloid accumulation. Through mediation analysis, the team further confirmed that reduced irisin levels are linked to greater amyloid accumulation, which in turn may lead to cognitive decline.

"Early diagnosis of Alzheimer's disease currently relies mainly on tests such as amyloid PET and cerebrospinal fluid analysis, which are costly and have limited accessibility," Kang said. "This study is meaningful in that it suggests the possibility of developing a blood-based biomarker that could screen for Alzheimer's risk early using only a blood irisin measurement."

He added that the study "confirmed in actual human subjects that irisin, which increases through exercise, is closely linked not only to muscle health but also to the core pathology of Alzheimer's disease," and expressed hope that the findings would serve as an important basis for developing blood-based biomarkers using irisin as well as dementia prevention strategies through exercise and improved muscle function.

The study is also significant for confirming the clinical relevance of the "muscle-brain axis" by analyzing blood biomarkers alongside amyloid PET imaging. The findings were recently published in Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, an international journal of the Alzheimer's Association.

Experts advise that these findings should be considered alongside existing research showing that regular exercise helps prevent dementia. While irisin measurement has not yet reached the stage of standard clinical use, technology that could assess dementia risk more easily and quickly through a simple blood test is expected to significantly broaden the scope of early diagnosis and preventive treatment.