Characterizing Lewy Pathology in 231 Essential Tremor Brains from the Essential Tremor Centralized Brain Repository
Elan Louis1, Sheng-Han Kuo2, Phyllis Faust2
1University of Texas Southwestern Medical Center, 2Columbia University Medical Center
Objective:
To address several questions: (1) What proportion of essential tremor (ET) cases exhibit Lewy pathology (LP)? (2) What is the nature (i.e., type, location, severity) of that pathology? (3) How does that pathology relate to various neurodegenerative conditions (e.g., Parkinson's disease [PD], Alzheimer’s type changes)? (4) What are the clinical correlates of that pathology?
Background:
The aforementioned questions have significant value in terms of furthering our understanding of the biological and mechanistic basis for ET. The Essential Tremor Centralized Brain Repository is the largest repository of prospectively-collected ET brains (n = 231). Hence, we are uniquely poised to address these questions.
Design/Methods:
Each brain had a complete neuropathological assessment, including assessment of LP with alpha-synuclein immunostaining. We created a 10-category classification scheme to fully encapsulate the patterns of LP observed. Four metrics of cerebellar pathology were also quantified.
Results:
Mean age at death = 89.0 ± 6.4 years. Fifty-eight (25.1%) had LP and 46 (19.9%) had early to late stages of pathologic PD. LP was very heterogeneous. Of 58 cases with LP, 14 (24.1%) clinically developed possible PD or PD after a latency of five or more years. There was a similar degree of cerebellar pathology in ET cases both with and without LP.
Conclusions:
One-in-four ET cases had LP, a proportion that in the context of other studies among control populations seems high. LP was heterogeneous, and likely a partial function of observed clinical associations between (1) ET and PD and (2) ET and Alzheimer’s disease, as well as other factors that are unknown. There was evidence of cerebellar degeneration in ET cases both with and without LP, rather than just without. These data have value in terms of furthering our understanding of the biological and mechanistic basis for ET as well as its relatedness to other degenerative diseases.