Characterizing Lewy Pathology in 231 Essential Tremor Brains From the Essential Tremor Centralized Brain Repository

Area of Science:

• Neuropathology
• Neurodegenerative Diseases
• Movement Disorders

Background:

• Essential Tremor (ET) is a common movement disorder with unclear underlying pathology.
• The co-occurrence of Lewy pathology (LP) in ET brains is not well-characterized.
• Understanding ET's neuropathological landscape is crucial for diagnosing and treating related conditions.

Purpose of the Study:

• To determine the prevalence and patterns of Lewy pathology (LP) in a large cohort of prospectively collected essential tremor (ET) brains.
• To investigate the relationship between LP, Parkinson disease (PD) development, and cerebellar pathology in ET cases.
• To explore the neuropathological overlap between ET and other neurodegenerative disorders.

Main Methods:

• Comprehensive neuropathological assessment of 231 prospectively collected ET brains, including α-synuclein immunostaining for Lewy pathology.
• Classification of LP patterns into a 10-category scheme.
• Quantification of four metrics of cerebellar pathology.

Main Results:

• Lewy pathology (LP) was identified in 25.1% (58/231) of ET cases.
• 19.9% (46/231) of ET cases showed varying stages of Parkinson disease (PD).
• Of those with LP, 24.1% (14/58) developed clinically diagnosed PD, often after a significant latency period. Cerebellar pathology was similar in ET cases with and without LP.

Conclusions:

• A significant proportion of essential tremor (ET) cases harbor Lewy pathology (LP), suggesting a potential neuropathological link between ET and Parkinson disease (PD).
• The heterogeneity of LP in ET brains may explain observed clinical associations with PD and Alzheimer disease.
• These findings enhance the understanding of ET's complex relationship with other neurodegenerative diseases.