Objective: To elucidate the distribution of comorbid neuropathology in multiple system atrophy (MSA) and its clinical correlation.

Background: Multiple protein accumulations are often present in neurodegenerative diseases, such as Lewy-related pathology in Alzheimer’s disease (AD) and AD pathology in Lewy body disease. However, the comorbid neuropathologies in MSA and their correlation with clinical symptoms remain poorly understood. Although a subset of MSA patients develops cognitive impairment, its cause is also not well understood.

Method: This study included 160 pathologically proven MSA patients in the Mayo Clinic Brain Bank. We reviewed the medical records to identify the age at onset and the presence of cognitive impairment during the clinical course. MSA patients were divided into two groups according to the age of onset: early-onset (<60 years; n = 95, female 45%) and late-onset (>60 years; n = 65, female 42%). We examined comorbid pathologies, including AD pathology, Lewy-related pathology, TDP-43 proteinopathy, argyrophilic grains (AG), cerebral amyloid angiopathy (CAA), and aging-related tau astrogliopathy (ARTAG). We defined the presence of AD pathology based on the Braak neurofibrillary tangle (NFT) stage and the Thal amyloid phase if both of them were 3 or more. We compared the frequency of each pathology between the two age groups and groups with cognitive impairment (n = 48) or without cognitive impairment (n = 112). We also examined the correlation between comorbid pathologies and disease duration.

Results: The Braak NFT stage and Thal amyloid phase were positively correlated with age at onset. Among co-pathologies, AD pathology, Lewy-related pathology, AG, and CAA were significantly more common in the late-onset group. The number of comorbid pathologies significantly increased with age at onset. The frequency of cognitive impairment was not significantly different between the early-onset and late-onset groups. Furthermore, there was no significant difference in the frequency of comorbid pathologies between the two groups with and without cognitive impairment. The number of comorbid pathologies did not correlate with disease duration.

Conclusion: In MSA, comorbid conditions increased with increasing age of onset. However, there was no correlation between disease duration or cognitive impairment and comorbid pathologies, suggesting that the MSA pathology itself may contribute to the disease rather than comorbid pathologies in MSA.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/comorbid-neuropathological-features-in-multiple-system-atrophy/