Alzheimer's disease and Lewy body dementia (LBD) — which includes dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) — are separate conditions, but in practice, they frequently overlap. Research suggests that up to half of all people with Alzheimer's also show signs of LBD-related brain changes, and more than half of people with LBD have Alzheimer's brain changes present as well. A new study from LBDA’s Research Center of Excellence at Mayo Clinic, Rochester takes a closer look at what happens when both kinds of brain changes are present at the same time — and the findings, while preliminary, raise important questions for people living with LBD and for researchers.

The study was published in March 2026 in the journal JAMA Network Open. To understand what the researchers found, it helps to know a little about the proteins involved. Alpha-synuclein is a protein that misfolds and clumps together in LBD and is associated with dysfunction and loss of brain cells. Tau is a protein that behaves similarly in Alzheimer's disease — when it accumulates abnormally, it forms tangles inside neurons that are closely linked to memory loss and cognitive decline. When both proteins are found together in the same brain, scientists call it copathology. The central question this study asked is whether that copathology accelerates disease progression — and whether it does so equally in everyone.

To find out, researchers drew on data from the Alzheimer's Disease Neuroimaging Initiative, or ADNI — a large, long-running research database focused on Alzheimer's disease. Participants were tracked over time using tau PET scans, a type of imaging that can detect abnormal tau protein buildup in the brain. They also had their spinal fluid tested for alpha-synuclein using a highly sensitive technique called a seed amplification assay, or SAA, which can detect misfolded alpha-synuclein with high accuracy. It is important to note that ADNI was designed to study Alzheimer's disease, not LBD — and by design excluded participants with Parkinson's disease or prominent LBD clinical features. The alpha-synuclein detected in these participants was essentially an incidental finding within an Alzheimer's-focused study. The researchers themselves caution that their findings may not generalize directly to people with primary LBD.

Among the 415 participants, 69 tested positive for alpha-synuclein. The results were striking. When both alpha-synuclein and tau pathology were present, tau accumulated far more rapidly than when either pathology appeared alone. This effect was particularly pronounced in women. The reported accumulation rates suggest women with both pathologies may accumulate tau dramatically faster than men with the same copathology — perhaps as much as 20 times faster — but this comparison comes with an important caveat. The SAA-positive female group included just 27 participants, which is a very small sample. These numbers need to be replicated in larger, independent studies before they can be taken as firm.

The incidental nature of the alpha-synuclein findings actually makes this result more thought-provoking, not less. If copathology can drive this kind of accelerated progression even in a cohort that wasn't selected for LBD, it raises an important clinical question: how many people currently on an Alzheimer's disease trajectory may have undetected LBD copathology quietly shaping their decline? Better tools for detecting both pathologies — and understanding how they interact — could meaningfully change how patients are diagnosed and monitored.

The findings also have direct implications for clinical trials. The study authors showed that accounting for both copathology and biological sex could make trials targeting tau significantly more efficient, potentially requiring far fewer participants to detect a treatment effect. That kind of efficiency matters — it could help move promising therapies from the laboratory to the medicine cabinet more quickly.

For people living with LBD, these findings should not be interpreted as findings about their own prognosis. The study was not designed with LBD cohorts in mind, and much more research is needed. But the question at the heart of this work — how do Alzheimer's and LBD pathology interact, and in whom does that interaction matter most — is one the LBD community has a deep stake in seeing answered. Every study that brings more precision to that question moves the field closer to care that is not just effective in general, but right for each individual person.

Learn more with LBD resources for individuals, care partners and LBD professionals.

REFERENCE:

Mak E, Fought AJ, Wiste HJ, et al. 2026. Sex-specific associations of α-synuclein pathology with tau accumulation. JAMA Network Open 9(3):e260461. doi:10.1001/jamanetworkopen.2026.0461