Differential immunophenotypes of neuronal cytoplasmic inclusions in the dentate gyrus of multiple system atrophy and their association with clinicopathological features

Although hippocampal pathologies of multiple system atrophy (MSA) and their association with dementia have been reported, no studies have reported clinicopathological differences among MSA patients with and without neuronal cytoplasmic inclusions (NCIs) in the dentate gyrus (dntNCIs). We investigated hippocampal NCI pathology in 18 MSA patient autopsies, focusing on phosphorylated alpha-synuclein (pAS)- and phosphorylated tau (pT)-positive dntNCIs. There were 8 MSA patients without and 10 with dntNCIs. The latter group was subclassified by immunophenotype: those with pAS-positive dntNCIs (pAS-dntNCI subtype), those with pT-positive dntNCIs (pT-dntNCI subtype), and those with both types of dntNCIs. MSA patients with dntNCIs survived longer with prolonged tracheostomy and had dementia more frequently than those without dntNCIs. The brain weights of patients with dntNCIs were lower than those without dntNCIs. The presence of dementia was similar among the dntNCI subtypes. The pAS-dntNCI subtype was associated with longer survival and smaller brain weights; the pT-dntNCI subtype exhibited more frequent tau pathologies than the pAS-dntNCI subtype. Thus, MSA with dntNCIs is a possible pathological subtype of longer survivors that correlates with longer disease duration, prolonged tracheostomy, and high frequency of dementia. Understanding clinicopathological differences in MSA patients with and without dntNCIs may lead to improved personalized management strategies.

Automated summary

Despite existing reports on hippocampal pathologies in multiple system atrophy (MSA) and their association with dementia, no studies have compared the clinical and pathological differences between MSA patients with and without neuronal cytoplasmic inclusions (NCIs) in the dentate gyrus. This study investigated the NCI pathology in 18 MSA patient autopsies and found that MSA patients with dntNCIs had longer survival, higher frequency of dementia, and lower brain weights compared to those without dntNCIs. Understanding these differences could lead to improved personalized management strategies.