Are PDD and DLB in the same disease spectrum? Approach from genetic study

Abstract

Parkinson disease (PD) is a neurodegenerative disorder characterized by tremor, rigidity, and bradykinesia due to the degeneration of dopaminergic neurons in the substantia nigra. PD also includes numerous non–motor symptoms and can progress to dementia, known as Parkinson disease with dementia (PDD). Dementia with Lewy bodies (DLB) is another neurodegenerative disorder, diagnosed by fluctuating cognition, visual hallucinations, REM sleep behavior disorder, and parkinsonism. The clinical and pathological overlap between PDD and DLB, especially the presence of Lewy bodies, has led to discussions on whether they lie on the same disease spectrum. Key genes implicated in PDD include SNCA, GBA1, and APOE. These genes are also involved in DLB, but recent genetic studies have highlighted additional genes linked to Alzheimer disease pathology and glucocerebrosidase function in DLB. Further genetic research helps elucidate the commonalities and differences between PDD and DLB, advancing our understanding and guiding the identification of therapeutic targets of these disorders.