Print This PostAt the time of writing (early 2026), a comprehensive search for “Dementia” and associated terms on PubMed will return over 35,000 articles. Alzheimer’s disease is the most common cause of dementia, is most commonly associated with dementia, and is one of the leading causes of death worldwide. Accordingly, a search for Alzheimer’s disease returns over 20,000 articles. Similarly, Parkinsons’ disease is a relatively common, rapidly growing neurodegenerative disease, and returns over 15,000 articles. Huge amounts of our attention and effort in dementia research are, not unreasonably, directed at the big topics and big diseases.
This is a problem though. In a world where there are thousands of papers being written every year in the field, it’s too easy to only focus on your particular niche of the literature. Rarely do people read papers on topics outside of their immediate research, let alone on different diseases entirely. Who has the time? But a fundamental feature of neurodegenerative diseases is their heterogeneity – Alzheimer’s, Parkinson’s, Frontal-Temporal disease… these are not uniform, monolithic diseases, but overlapping conditions sharing biological mechanisms and pathologies. In this light, Lewy Body Disease, which only returns about 1000 results on PubMed, is important, and deserves more attention.
Lewy bodies are clumps of aggregated proteins and other cellular materials that can build up inside certain neurons. They are named after the pathologist who was among the first to describe them, Dr. Friedrich Lewy. The key protein associated with them is alpha-synuclein: when alpha-synuclein misfolds and aggregates, it seems to form these highly organised Lewy body structures (and related deposits like Lewy neurites). This pathological hallmark links a set of conditions together into what are called synucleinopathies.
Lewy bodies do not seem to be a harmless sideshow. They are associated with cell death, their formation appears to be damaging to neurons, and they seem to indicate unhealthy cells. They are tied to changes in brain chemistry and circuits that affect thinking, movement, behaviour, mood, and sleep– the full messy spectrum of what makes neurodegenerative disease so difficult for people living with it and those supporting them.
Lewy bodies are most commonly associated with Parkinson’s disease – partly because Parkinson’s is relatively common and culturally visible. However, Lewy body disease is more general than just Parkinson’s, and refers to other neurodegenerative conditions driven by Lewy pathology. Clinically, this most often presents as a spectrum that includes dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), conditions that share core features such as cognitive fluctuations, visual hallucinations, parkinsonism (the movement symptoms associated with Parkinson’s disease), and REM sleep behaviour disorder.
[Naming and terminology is complex and convoluted across dementia research, but here it is especially mind-bendingly convoluted, a product of different ideas and discoveries building up and being revised over time, to the point of not necessarily making sense anymore. It’s not just you that finds this confusing and hard to follow, and not everyone agrees on the nomenclature anyway.]
Lewy Body disease, however, is important, not merely an add-on to Parkinson’s. It is one of the more common causes of dementia, and yet it remains underdiagnosed and frequently misdiagnosed, with meaningful consequences for patient care and safety. One particularly important issue is medication sensitivity: people with Lewy body dementia can have severe (and sometimes life-threatening) reactions to antipsychotic/neuroleptic drugs, so clinicians have to prescribe these medications with extreme caution.
So how did I, an Alzheimer’s disease researcher focused on tau pathology, cross the boundary and become familiar with Lewy body disease? In a world of siloed research, I wanted to build bridges across diseases, and in my PhD, I compared both Alzheimer’s and Parkinson’s disease. I initially expected to be studying tau in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease, but discovered that alpha synuclein pathology, i.e., Lewy body pathology, was all too common in Alzheimer’s disease too.
Recent reviews suggest that more than half of all Alzheimer’s disease cases – typically defined by the presence of amyloid plaques, tau tangles, and neurodegeneration – have Lewy bodies too. That doesn’t mean every person with Alzheimer’s has Lewy bodies. However, it does mean that if we are working on Alzheimer’s and never considering the influence of concomitant Lewy body disease, we are probably missing a big piece of the biological reality.
For my PhD, Lewy bodies in Alzheimer’s disease went from being an awkward piece of data I was trying to explain away to a core question of my research and a central narrative in my thesis. Why do Lewy bodies emerge so frequently in Alzheimer’s disease? What causes them to arise? What role do they play? Can we model them in cells in the lab? What do they mean for patients?
This is no mere academic curiosity. Large-scale neuropathology work repeatedly underlines that co-occurring pathologies are the norm in the aged brain, and that the complex presentation of dementia often does not come from a single cause, but reflects the accumulation and interaction of multiple different biologies that we have typically thought of as being distinct diseases. That is to say, neurodegenerative diseases are becoming increasingly recognised as heterogenous. One person with Alzheimer’s disease may have a brain that looks, pathologically, completely unalike another patient’s.
If you recruit an “Alzheimer’s” cohort for a trial, but a meaningful number of your participants (say, half, for example…), have substantial Lewy body disease (and some have vascular injury, and others have TDP-43/LATE pathology, etc.), then you don’t have one biological population. You have a mixture of different people with different variants of disease. And mixtures are notoriously good at diluting effects of treatments specialised to one aspect of the disease.
This is where biomarkers come in. Biomarkers aren’t only about earlier diagnosis; they’re about better definition of what makes up each patient’s unique profile of disease – personalised medicine. One genuinely encouraging sign is that major definitions and framework documents are increasingly tackling this. In the 2024 revision of the Alzheimer’s Association workgroup criteria, the authors explicitly expand beyond the classic AT(N) framing and introduce additional biomarker categories — including alpha-synucleinopathy (“S”) — noting that vascular and synuclein biomarkers are relevant because Alzheimer’s disease often occurs with co-pathologies in older adults.
Lewy body disease matters to all neurodegenerative disease researchers because the pathways it implicates and the syndromes it appears in touch many of the biggest and most salient diseases in the dementia field. But Lewy body disease is also more than just a complicating supporting character in the Alzheimer’s dementia story. Many people are living with Lewy body dementia, and it is too often missed, misdiagnosed, or diagnosed late, with real consequences for management and support. And unlike some of the more headline-grabbing areas of dementia treatment development, there is still no disease-modifying therapy for DLB/LBD — which makes the attention gap feel even harder to justify.
So, if ever there was a time to broaden the horizons of your reading and your research, this is certainly it. A time when we are increasingly aware of how flimsy (and possibly fabricated) the boundaries are between diseases.
Studying Lewy pathology in Alzheimer’s disease might help us understand heterogeneity, refine cohorts, and design better trials, and give us more ideas about how other pathologies work in parallel or in combination. But it is also clear that Lewy body disease itself is common enough, serious enough, and under-recognised enough to merit far more research focus than it currently gets. It is a core part of the dementia landscape and deserves attention.
Ajantha Abey
Author
Dr Ajantha Abey is a Postdoctoral Researcher in the Kavli Institute at University of Oxford. He is interested in the cellular mechanisms of Alzheimer’s, Parkinson’s, and other diseases of the ageing brain. Previously, having previoulsy explored neuropathology in dogs with dementia and potential stem cell replacement therapies. He now uses induced pluripotent stem cell derived neurons to try and model selective neuronal vulnerability: the phenomenon where some cells die but others remain resilient to neurodegenerative diseases.
Dementia Researcher
Dr Yvonne Couch
Dr Sam Moxon
Rahul Sidhu
