Differentiating Pathologic Features of Alzheimer Disease and Lewy Body Dementia: Charbel Moussa, MBBS, PhD

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"[Patients with] Alzheimer disease tend to not have motor symptoms. In [patients with] Lewy body dementia, their chief medical complaint is dementia, but they do develop some aspects of a motor disorder in 1 or 2 years that is reminiscent of Parkinson disease. In both cases, the diagnosis initially might be similar, overlapping, or hard to differentiate."

Alzheimer disease (AD) and Lewy body dementia (LBD) are common neurodegenerative disorders that frequently present with cognitive decline but differ in their underlying pathology, clinical trajectory, and therapeutic considerations. Although both conditions may feature overlapping symptoms and, in some cases, overlapping brain pathology, distinguishing between them has important implications for diagnosis, prognosis, and management. Advances in biomarker development, particularly amyloid and tau positron emission tomography and blood-based assays, have refined the approach to AD. In addition, tools such as dopamine imaging have helped clarify the role of synuclein-related pathology in LBD and related movement disorders.

At the recently conlcuded 5th Annual Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress, held by the PMD Alliance from June 4-8, 2026, dementia expert Charbel Moussa, MBBS, PhD, presented a talk titled “Alzheimer’s Disease and Lewy Body Dementia: Differentiating Pathologies to Determine Therapies.” In his presentation, Moussa, professor of neurology at Georgetown University Medical Center, outlined the overlapping yet distinct pathologic features of AD and LBD, emphasizing the roles of amyloid, tau, and α-synuclein, as well as differences in dopaminergic neurotransmission. He also discussed how these mechanistic differences may inform diagnostic strategies and the development of targeted therapies.

In a follow-up interview with NeurologyLive^®, Moussa expanded on key points from his talk. In the video segment, he explained how AD is characterized by tau and amyloid plaques and tangles, whereas Lewy body dementia is primarily an α-synucleinopathy with marked dopamine deficiency, more closely aligned with Parkinson disease. He described how amyloid and tau imaging and blood tests can support diagnosis in both conditions but do not differentiate them, whereas dopamine imaging serves as a critical tool for identifying LBD. Moussa also reviewed the overlapping early clinical presentations and underscored how differences in motor symptoms, executive dysfunction, behavioral disturbances, and disease progression emerge over time to help distinguish AD from LBD in clinical practice.

Click here for more coverage of ATMRD 2026.

REFERENCES
1. Moussa C. Alzheimer’s Disease and Lewy Body Dementia: Differentiating Pathologies to Determine Therapies. Presented at: ATMRD Congress 2026; June 4-8, 2025; Washington, DC.