May 07, 2025
People with dementia with Lewy bodies (DLB), Parkinson’s disease (PD), or multiple system atrophy (MSA) all commonly experience REM sleep behavior disorder (RBD) as an early stage of their later disease. Approximately half of people with RBD will develop DLB, half will develop PD, and a small number will develop MSA. However, it is not yet clear why some individuals with RBD develop DLB instead of PD or MSA. A group of researchers from Canada has recently shown evidence that the presence of proteins associated with Alzheimer’s disease (AD) may hold the key.
Why study AD proteins in diseases associated with alpha-synuclein?
While the main protein associated with DLB and PD is misfolded alpha-synuclein, many people with DLB or PD also have significant amounts of abnormal proteins associated with Alzheimer’s disease (AD). For example, past studies have shown that up to half of people with DLB and PD also have beta-amyloid plaques, a brain change most commonly associated with AD. It is also common for these folks to have abnormal tau protein, which is associated closely with AD, but also with other neurodegenerative diseases. Having these AD-related proteins is more common in DLB than PD and is thought to lead to an earlier age of symptom onset, faster decline, and decreased lifespan. However, this had not yet been studied in early disease stages, such as RBD.
What did the researchers do?
The researchers studied over 140 volunteers with RBD, none of whom yet had a diagnosis of DLB or PD, and all of whom provided a blood sample. From the blood samples, researchers measured both the ratio of Aβ42/40 (lower levels in blood are associated with increasing beta-amyloid levels in the brain) and pTau181, a measure of misfolded tau protein associated with AD.
In addition, volunteers took cognitive tests throughout the study. The researchers followed participants over time to see who developed DLB or PD and whether there were any relationships between the AD markers, cognitive testing, and whether a person developed DLB or PD.
What did the study team find?
Of the 142 volunteers included in the analysis, 32 developed either DLB (18), PD (13) or MSA (1) within the period of the study.
For the 18 volunteers who later developed DLB, their initial blood levels of beta-amyloid and tau were significantly worse than those who did not develop DLB. While group sizes in this study were relatively small, the size of the effect was quite pronounced. People with low (worse) beta-amyloid in their blood were 10 times more likely to develop DLB during the period of the study, and those with high (worse) pTau181 were 15 times more likely.
For the 13 volunteers who later developed PD, the signals were somewhat less clear. Low blood levels of beta-amyloid were associated with later development of PD, but not as strongly as for DLB. Moreover, pTau181 did not differ between those who developed PD and those who did not.
Digging deeper, the researchers examined levels of these blood markers for AD in people who developed PD with mild cognitive impairment (PD-MCI). Levels of beta-amyloid were lower (worse) in people with PD-MCI, but again, pTau181 was not associated with development of PD-MCI. In contrast, for people who developed PD without MCI, there were no differences in their initial levels of beta-amyloid or pTau18.
In addition, many of the cognitive tests that volunteers completed during the study correlated with their blood levels of beta-amyloid and tau, further suggesting a link between these AD-associated proteins and the development of cognitive decline in people with RBD.
So, what does it all mean?
Taken together, these data are consistent with the idea that the early presence of misfolded proteins associated with Alzheimer’s disease could be an important indicator of what the future may hold for a person with RBD. The data suggest that individuals with RBD may be more likely to develop DLB if they already have some positive markers for AD, and if they develop PD instead, it is more likely to be PD with MCI than PD without MCI.
Will this change what happens at my doctor’s office?
Not yet. The data in this paper are important but need to be verified in larger groups and by multiple laboratories before they might change medical practice. It is possible that in the future, a medical workup for RBD might include measures of AD-associated blood markers to determine if or when a person may develop DLB or PD-MCI. This study also suggests that in the future we may be able to treat people who have RBD and AD markers with one of the FDA-approved medications for lowering beta-amyloid levels to prevent or delay the progression from RBD to DLB or PD-MCI. However, that would need to be tested in large, well-controlled clinical trials to know whether it would be safe or effective.
How can I get involved?
Understanding the disease processes underlying Lewy body dementia takes research, and research takes people like you.
For more information on clinical trials and other studies that might be right for you, LBDA encourages you to visit our clinical trials page. To stay up-to-date on new studies when they launch, you can also sign up for LBDA’s Lewy Trial Tracker.
REFERENCE
Delva A, Pelletier A, Somerville E, Montplaisir J, Gagnon JF, Kollmorgen G, Kam-Thong T, Kustermann T, Machado V, Gan-Or Z, and Postuma RB. 2025. Plasma pTau181 and amyloid markers predict conversion to dementia in idiopathic REM sleep behaviour disorder. Brain, online ahead of print. DOI: 10.1093/brain/awaf003.