Evoking a Reaction: Alzheimer’s Disease, Sex and Astrocytes

Abstract

Alzheimer’s disease is a neurodegenerative disorder with no current cure. Even though women are significantly more affected, the disease has global reach, as 55 million people are suffering from it worldwide. Alzheimer’s disease is still not entirely understood but an important factor is the accumulation of a small protein (amyloid-beta) which grows into larger plaques throughout the brain. Astrocytes, a cell-type involved in maintaining the central nervous system, are significantly affected by this accumulation. As a result, astrocytes go into an altered, reactive state. The implication of this state is not entirely clear, but changes in gene expression point towards a less neuroprotective profile. Like in Alzheimer’s diseases, sex differences are observed within astrocytes as well. The relationship between reactive astrocytes, sex and Alzheimer’s disease might thus be an important link in understanding the disease. Therefore, this study performed a visual, exploratory analysis on male and female mouse brains, comparing astrocytes between healthy brains and brains expressing amyloid-beta plaques. Significant spatial relationships between amyloid-beta plaques and reactive astrocytes were observed. Astrocyte reactivity, as well as increases in astrocyte amounts, was somewhat concentrated to a particular brain region (the dentate gyrus). Finally, no significant sex differences were found but further steps have been suggested. This study therefore confirmed a relationship between astrocytes and amyloid-beta plaques and indicated several follow-up studies. Overall, we provided relevant information regarding a relationship that is still not entirely understood which might be important in, not only understanding Alzheimer’s Disease, but also finding a cure.