Houston Methodist Neurologist Explains the Importance of Studying Co-Pathologies in Neurodegenerative Diseases

Dr. Jon B. Toledo, is an Assistant Professor of Neurology, who focuses on studying Lewy body disease, Alzheimer’s disease and the overlap of different neurodegenerative and non-neurodegenerative diseases. Dr. Toledo discussed with Leading Medicine why co-pathologies are critically important to study in neurodegenerative diseases. The presence of multiple distinct disease-related proteins in a single patient is common and is the reason why single-target therapies often fail. A shift is required towards greater awareness about co-pathologies to create solutions with precision medicine and combination therapies.

Here are Dr. Toledo’s thoughts on this topic.

Q: Why are co-pathologies critically important to study in neurodegenerative diseases?

A: Neurodegenerative diseases such as Alzheimer’s and Lewy body disease co-occur frequently. Around one-third of Alzheimer’s disease patients have Lewy pathology, and about half of the patients who have dementia with Lewy bodies have the pathology of Alzheimer’s. Individuals with Lewy body disease (LBD) or Parkinson's disease can develop Alzheimer's pathology, and vice versa. For example, Lewy pathology or abnormal α-synuclein protein clumps (a hallmark of LBD) can also be present in Alzheimer’s patients. Co-pathologies significantly alter disease progression and presentation, drive cognitive decline, and affect treatment responses, making clinical diagnoses more challenging. There is an urgent need for personalized, combination therapies targeting multiple proteinopathies, rather than single targets and novel, mechanism-based interventions.

For further information on neurodegenerative diseases and Dr. Toledo’s work on this topic, please see the following papers:

Jon B. Toledo, David P Salmon, Melissa J Armstrong, Douglas Galasko. Cognitive decline profiles associated with Lewy pathology in the context of Alzheimer's disease neuropathologic change. Alzheimer's Res Ther. 2024 Dec 20;16(1):270. doi: 10.1186/s13195-024-01628-z.

Di Wang, Nicolas Honnorat, Jon B Toledo, Karl Li, Sokratis Charisis, Tanweer Rashid, Anoop Benet Nirmala, Sachintha Ransara Brandigampala, Mariam Mojtabai, Sudha Seshadri, Mohamad Habes. Deep learning reveals pathology-confirmed neuroimaging signatures in Alzheimer's, vascular and Lewy body dementias. Brain. 2025 Jun 3;148(6):1963-1977. doi: 10.1093/brain/awae388.

Jon B Toledo, Carla Abdelnour, Rimona S Weil, Daniel Ferreira, Federico Rodriguez-Porcel, Andrea Pilotto, Kathryn A Wyman-Chick, Michel J Grothe, Joseph P M Kane, Angela Taylor, Arvid Rongve, Sonja Scholz, James B Leverenz, Bradley F Boeve, Dag Aarsland, Ian G McKeith, Simon Lewis, Iracema Leroi, John P Taylor; ISTAART Lewy body dementias Trial Methods Working Group. Dementia with Lewy bodies: Impact of co-pathologies and implications for clinical trial design. Alzheimers Dement. 2023 Jan;19(1):318-332. doi: 10.1002/alz.12814.