Astrogliosis and sexually dimorphic neurodegeneration and microgliosis in the olfactory bulb in Parkinson's disease

Hyposmia is prodromal, and male sex is a risk marker for an enhanced likelihood ratio of Parkinson's disease. The literature regarding olfactory bulb volume reduction is controversial, although the olfactory bulb has been largely reported as an early and preferential site for alpha-synucleinopathy. These pathological deposits have been correlated with neural loss in Nissl-stained material. However, microgliosis has rarely been studied, and astrogliosis has been virtually neglected. In the present report, alpha-synucleinopathy (alpha-synuclein), neurodegeneration (Neu-N), astrogliosis (GFAP), and microgliosis (Iba-1) were quantified, using specific markers and stereological methods. Disease, sex, age, disease duration, and post-mortem interval were considered variables for statistical analysis. No volumetric changes have been identified regarding disease or sex. alpha-Synucleinopathy was present throughout the OB, mainly concentrated on anterior olfactory nucleus. Neurodegeneration (reduction in Neu-N-positive cells) was statistically significant in the diseased group. Astrogliosis (increased GFAP labeling) and microgliosis (increased Iba-1 labeling) were significantly enhanced in the Parkinson's disease group. When analyzed per sex, neurodegeneration and microgliosis differences are only present in men. These data constitute the demonstration of sex differences in neurodegeneration using specific neural markers, enhanced astrogliosis and increased microgliosis, also linked to male sex, in the human olfactory bulb in Parkinson's disease.

Automated summary

Hyposmia is an early symptom of Parkinson's disease, with male gender being a risk factor. The reduction of olfactory bulb volume is controversial, but it is considered an early and preferential site for alpha-synucleinopathy. Neurodegeneration and microgliosis differences are only present in men, suggesting sex differences in neurodegeneration in the human olfactory bulb in Parkinson's disease.