Quantitative Assessment of Pathological Tau Burden in Essential Tremor: A Postmortem Study

Area of Science:

• Neuropathology
• Neurodegenerative Diseases
• Cognitive Impairment

Background:

• Essential tremor (ET) patients exhibit increased cognitive impairment and dementia compared to controls.
• Limited neuropathological data exists for cognitive changes in ET.

Purpose of the Study:

• To investigate the neuropathological basis of cognitive impairment in Essential Tremor.
• To compare tau and other pathologies in postmortem brains of ET cases and controls.

Main Methods:

• Postmortem brain tissue analysis from 26 ET cases and 73 controls.
• Assessment of tau pathology (NFTs), beta-amyloid, and Lewy bodies.
• Correlation of neuropathology with cognitive status (normal, mild cognitive impairment, dementia).

Main Results:

• Similar overall burdens of Braak, beta-amyloid, and Lewy body pathology between ET and control groups.
• Significantly higher neurofibrillary tangle (NFT)-positive neurons in the neocortex of ET cases compared to controls, irrespective of cognitive status (normal or MCI).
• No significant difference in NFT-positive neurons in the medial temporal lobe between ET and controls; cognitive function correlated with NFT counts.

Conclusions:

• Essential tremor is associated with increased tau pathology in the neocortex, preceding dementia.
• This suggests a potential predisposition to tau-related neuropathology in ET, contributing to cognitive decline.
• Neocortical tau burden, not medial temporal lobe pathology, differentiates ET from controls in pre-dementia stages.