More frequent Lewy bodies but less frequent Alzheimer-type lesions in multiple system atrophy as compared to age-matched control brains

Excerpt

Multiple system atrophy (MSA), a largely sporadic adult-onset progressive synucleinopathy, is divided into two clinicopathologic subtypes: MSA-P [striatonigral degeneration (SND) with predominant Parkinsonian features] and MSA-C [olivopontocerebellar atrophy (OPCA) with predominant cerebellar ataxia], whereas autonomic dysfunction common to all forms of MSA and referred to previously as Shy-Drager syndrome (SDS), has been discouraged in the new consensus criteria [6]. Neuropathology, in addition to multisystem neurodegeneration involving the striatonigral and the ponto-cerebello-olivary systems in variable degrees and overlap [10], is hallmarked by α-synuclein positive glial cytoplasmic inclusions (GCI) mainly in oligodendroglia, the demonstration of which is required in the diagnosis of definite MSA and cause anatomically selective neuronal loss, gliosis, and myelin pathology [13]. Less frequent neuronal and astroglial cytoplasmic inclusions of similar composition, rare ubiquitin-positive neuronal nuclear or cytoplasmic inclusions resembling those in motoneuron disease, and ubiquitin-positive neuritic degeneration resembling neuropil threads but being tau-negative are seen in affected areas [13]. All these inclusions contain insoluble α-synuclein filaments [13], a subset of GCIs contains tau and 14-3-3 protein [5], which, together with other components, are also present in Lewy bodies (LB), the morphologic hallmarks of Parkinson disease (PD) and dementia with Lewy bodies (DLB) [12]. However, only a few reports have described the co-existence of GCIs and LBs (see [17, 18, 20, 26]). In the MSA cohort examined by Wenning et al. [26] with a mean age at death of 62.7 years the total prevalence of LBs was 20.3% (5/35 in substantia nigra and 3 in the neocortex), while Ozawa et al. [18] reported LBs in the brainstem in 7/94 cases (10.6%), but did not mention Alzheimer-related changes. …