Unique Lewy pathology in myotonic dystrophy type 1

Area of Science:

• Neuropathology
• Neurodegenerative Diseases
• Genetics

Background:

• Lewy body-related α-synucleinopathy (Lewy pathology) is a hallmark of Lewy body dementias.
• Previous reports suggest Lewy pathology in myotonic dystrophy type 1 (DM1), but its prevalence and characteristics remain underexplored.

Purpose of the Study:

• To determine the prevalence and anatomical distribution of Lewy pathology in genetically confirmed DM1 cases.
• To compare Lewy pathology in DM1 with control cases and investigate its deviation from established pathological paradigms.

Main Methods:

• Autopsy brain and peripheral nervous system tissues from 32 DM1 patients and controls were analyzed.
• Immunohistochemistry was used to detect α-synuclein deposits, following the Dementia with Lewy Bodies Consensus Guideline with expanded anatomical sites.

Main Results:

• Lewy pathology was detected in 34.4% of DM1 cases, significantly higher than the 20.1% in controls.
• Lewy pathology in DM1 was widespread but showed a unique distribution, with sparse involvement of the substantia nigra, amygdala, and cerebral cortex.
• The observed Lewy pathology pattern in DM1 did not align with Braak's staging or the olfactory-amygdala pathway.

Conclusions:

• This study provides the first detailed description of unique Lewy pathology in DM1.
• The distinct characteristics of Lewy pathology in DM1 may offer novel insights into α-synuclein propagation mechanisms in neurodegenerative diseases.