Jie J Pan1, Michelle Lee2, Lawrence S Honig3, Jean-Paul G Vonsattel4, Phyllis L Faust5, Elan D Louis6. 1. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA. 2. G.H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA. 3. G.H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA. 4. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA. 5. Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA. 6. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA; G.H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: EDL2@columbia.edu.
Abstract
BACKGROUND: In addition to tremor, patients with essential tremor (ET) may exhibit non-motor features, including a range of cognitive deficits. Several prospective, population-based epidemiological studies have reported an association between ET and incident dementia, especially Alzheimer's disease (AD). Moreover, in a brain repository-based study, a larger than expected proportion of ET patients also developed pathological changes characteristic of progressive supranuclear palsy, further suggesting a link between ET and tau pathology. METHODS: We selected a group of ET patients that were free of dementia clinically and without AD on postmortem examination. Our hypothesis was that neuronal tauopathic burden would be higher in the brains of these ET patients compared to controls. We compared Braak stage for neuronal tangles and Consortium to Establish a Registry for Alzheimer's Disease (CERAD) scores for neuritic plaques in the two groups. RESULTS: The two groups were similar in age (82.6 ± 6.0 vs. 80.4 ± 8.1, p = 0.22). The 40 ET patients had a higher Braak neurofibrillary stage than 32 controls (means: 2.2 ± 1.2 vs. 1.2 ± 1.1; medians: 2.0 vs. 1.0, p < 0.001). Meanwhile, CERAD scores for neuritic plaques were similar in patients and controls (means: 0.6 ± 0.9 vs. 0.5 ± 0.6; medians: 0.0 vs. 0.0, p = 0.83). CONCLUSION: While ET itself is not a tauopathy (i.e., a neurodegenerative disorder among whose main features are accumulation of hyperphosphorylated tau protein), ET may predispose individuals to accumulate more widespread cellular tau aggregates, and thus tau could play a central role in the cognitive impairment that can accompany ET.
BACKGROUND: In addition to tremor, patients with essential tremor (ET) may exhibit non-motor features, including a range of cognitive deficits. Several prospective, population-based epidemiological studies have reported an association between ET and incident dementia, especially Alzheimer's disease (AD). Moreover, in a brain repository-based study, a larger than expected proportion of ETpatients also developed pathological changes characteristic of progressive supranuclear palsy, further suggesting a link between ET and tau pathology. METHODS: We selected a group of ETpatients that were free of dementia clinically and without AD on postmortem examination. Our hypothesis was that neuronal tauopathic burden would be higher in the brains of these ETpatients compared to controls. We compared Braak stage for neuronal tangles and Consortium to Establish a Registry for Alzheimer's Disease (CERAD) scores for neuritic plaques in the two groups. RESULTS: The two groups were similar in age (82.6 ± 6.0 vs. 80.4 ± 8.1, p = 0.22). The 40 ETpatients had a higher Braak neurofibrillary stage than 32 controls (means: 2.2 ± 1.2 vs. 1.2 ± 1.1; medians: 2.0 vs. 1.0, p < 0.001). Meanwhile, CERAD scores for neuritic plaques were similar in patients and controls (means: 0.6 ± 0.9 vs. 0.5 ± 0.6; medians: 0.0 vs. 0.0, p = 0.83). CONCLUSION: While ET itself is not a tauopathy (i.e., a neurodegenerative disorder among whose main features are accumulation of hyperphosphorylated tau protein), ET may predispose individuals to accumulate more widespread cellular tau aggregates, and thus tau could play a central role in the cognitive impairment that can accompany ET.
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