4.6 Article

Neocortical Neuronal Loss in Patients with Multiple System Atrophy: A Stereological Study

Journal

CEREBRAL CORTEX
Volume 27, Issue 1, Pages 400-410

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhv228

Keywords

glial cells; multiple system atrophy; neocortex; neurons; stereology

Categories

Funding

  1. Velux Foundation [VELUX26781]
  2. Danish Parkinson's Disease Association
  3. Augustinus Foundation [10-3820]
  4. Lundbeck Foundation [2012-12359]
  5. Bispebjerg Hospital Research Foundation
  6. Danish Movement Disorder Society
  7. John and Birthe Meyer Foundation
  8. Jascha Foundation

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To determine the extent of neocortical involvement in multiple system atrophy (MSA), we used design-based stereological methods to estimate the total numbers of neurons, oligodendrocytes, astrocytes, and microglia in the frontal, parietal, temporal, and occipital cortex of brains from 11 patients with MSA and 11 age-and gender-matched control subjects. The stereological data were supported by cell marker expression analyses in tissue samples from the prefrontal cortex. We found significantly fewer neurons in the frontal and parietal cortex of MSA brains compared with control brains. Significantly more astrocytes and microglia were observed in the frontal, parietal, and temporal cortex of MSA brains, whereas no change in the total number of oligodendrocytes was seen in any of the neocortical regions. There were significantly fewer neurons in the frontal cortex of MSA patients with impaired executive function than in patients with normal executive function. Our results indicate that the involvement of the neocortex in MSA is far more widespread and substantial than previously thought. In addition, our results suggest that the increasingly recognized cognitive impairment in MSA may be related to neuronal loss in the frontal cortex.

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