Scientists have found a way to detect signs of Lewy body disease in living people, including some who have no obvious memory or movement problems.
The discovery could eventually help doctors identify the disease much earlier than is usually possible today.
Lewy body disease is linked to both dementia with Lewy bodies and Parkinson’s disease. It develops when a protein called alpha-synuclein forms abnormal clumps inside brain cells, interfering with the way the cells work.
These clumps are known as Lewy bodies. Depending on where damage develops in the brain, people may experience problems with movement, memory, thinking, attention, sleep and other important functions.
Diagnosing Lewy body disease has traditionally been difficult because several brain disorders can cause similar symptoms. In the past, definite confirmation of Lewy bodies generally required examination of brain tissue after death.
Researchers at Lund University in Sweden studied whether a newer laboratory method could detect abnormal alpha-synuclein while people were still alive. The test examines cerebrospinal fluid, the clear liquid that surrounds the brain and spinal cord.
The scientists studied more than 1,100 people from the Swedish BioFINDER-2 study who did not have problems with thinking or movement when they entered the research. Surprisingly, nearly 10% tested positive for abnormal alpha-synuclein.
This suggests that biological changes connected to Lewy body disease can exist before the symptoms normally used to diagnose the condition become noticeable. Finding the disease during this early stage could become especially important if treatments are developed that can slow or stop its progression.
The researchers also discovered that people with abnormal alpha-synuclein tended to perform worse on tests of their sense of smell. This happened even though the participants otherwise appeared healthy, supporting earlier evidence that loss of smell can be an early sign of diseases involving alpha-synuclein.
The team suggested that smell testing could potentially become one part of a future screening approach for older adults. People with a poor sense of smell might then undergo more specific testing, although much more research is needed before such screening could be recommended for the general population.
Another important finding involved Alzheimer’s disease. Some participants had biological signs of both Lewy body disease and Alzheimer’s, showing that more than one disease process can occur in the brain at the same time.
This overlap may help explain why dementia can progress differently from one person to another. Identifying the biological changes behind a person’s symptoms could eventually allow doctors to make more precise diagnoses and choose treatments that target the right disease.
The cerebrospinal fluid test is promising, but collecting this fluid requires a lumbar puncture, sometimes called a spinal tap. A simple blood test would be easier to use widely, but detecting abnormal alpha-synuclein in blood is more difficult because the amounts are much smaller.
The findings do not mean that everyone who tests positive will definitely develop dementia or Parkinson’s disease. Researchers still need long-term studies to understand how often people with these early biological changes develop symptoms and how quickly that happens.
The research from Lund University was published in the peer-reviewed journal Nature Medicine in 2023. The studies used a technique called an alpha-synuclein seed amplification assay to identify abnormal forms of the protein associated with Lewy body disease.
Scientists are now developing treatments designed to target abnormal alpha-synuclein and other processes involved in neurodegenerative disease. Earlier and more accurate testing could become crucial because treatments that protect brain cells may work best before extensive damage has occurred.
For now, the discovery represents an important step toward understanding the hidden early stages of Lewy body disease. It also raises the possibility that doctors may one day be able to identify the disease before major memory or movement problems begin.
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