Morphological differences between the two major subtypes of multiple system atrophy with cognitive impairment

Area of Science:

• Neuropathology
• Neurodegenerative Diseases
• Multiple System Atrophy

Background:

• Multiple system atrophy (MSA) is a progressive neurodegenerative disorder with two main phenotypes: parkinsonism-predominant (MSA-P) and cerebellar ataxia-predominant (MSA-C).
• Cognitive impairment is a recognized feature in MSA, but its neuropathological underpinnings, particularly in relation to distinct phenotypes and co-existing pathologies, require further elucidation.

Purpose of the Study:

• To compare the neuropathological features of alpha-synuclein and Alzheimer pathologies between MSA-P and MSA-C.
• To investigate the association between neuropathological findings and cognitive impairment in different MSA phenotypes.

Main Methods:

• Neuropathological examination of 35 MSA-P and 15 MSA-C cases.
• Semiquantitative evaluation of alpha-synuclein, tau, amyloid-beta (Aβ) load, cerebral amyloid angiopathy (CAA), and Lewy co-pathology.
• Correlation of neuropathological findings with clinical presentation, including cognitive status.

Main Results:

• MSA-P cases demonstrated significantly higher alpha-synuclein pathology in the cortex and brainstem compared to MSA-C.
• Tau load was slightly higher in MSA-P with cognitive impairment, whereas Aβ load and CAA were more prominent in MSA-C.
• Lewy co-pathology was more frequent in MSA cases with cognitive decline but did not differ between MSA-P and MSA-C.

Conclusions:

• Neuropathological differences exist between MSA-P and MSA-C, particularly concerning tau and amyloid deposition.
• These findings align with clinical observations of more severe cognitive dysfunction in MSA-P.
• Further research is needed to fully understand the pathobiological basis of cognitive impairment in MSA phenotypes.