The human olfactory bulb in Huntington's disease: sex-specific differences in volume and gliosis

Huntington's disease is a multisystemic neurodegenerative disorder for which increasing evidence suggests early involvement of brain regions beyond the primarily affected motor areas of the brain, such as the olfactory bulb, which is affected by multiple neurodegenerative diseases. However, the involvement of the olfactory bulb in Huntington's disease and the possible effects of sex on olfactory bulb characteristics in Huntington's disease patients remain poorly understood. In this study, volumetric and glial alterations in the olfactory bulbs of male and female Huntington's disease patients were stereologically analyzed and compared. A total of 30 fixed olfactory bulb samples from nondiseased and diseased patients were used. Histological, immunohistochemical (glial markers) and stereological methods were applied to evaluate volume and gliosis in the whole olfactory bulb and its different layers. The volumes of the whole olfactory bulb and its layers were similar in females and males with Huntington's disease. A negative correlation between volume and Vonsattel grade was observed for the stratum album and the anterior olfactory nucleus only in females. There is a significant astrogliosis only in female patients with Huntington's disease. Significant microgliosis was detected in the total population (males and females) in the diseased group compared with the nondiseased group. These findings suggest that the olfactory bulb, particularly the stratum album and the anterior olfactory nucleus, is affected in Huntington's disease and reveal sex-specific differences in volume and glial pathology, which highlights the importance of including biological sex as a critical variable in future research.