Understanding the Choroid Plexus in Alzheimer’s Disease

To unveil the choroid plexus transcriptional changes during Alzheimer’s disease and understand how the renin angiotensin system in the choroid plexus contributes to pathology and cognitive decline.

The renin-angiotensin system may play an important role in the progression of pathology in Alzheimer’s disease. In this proposal, we will look at the choroid plexus, a small tissue within the brain that makes the cerebrospinal fluid, as a novel source contributing to the local brain renin angiotensin system and cognitive decline in AD. Since there are likely a lot more changes happening in the choroid plexus other than the renin angiotensin system, we will also establish a comprehensive database of the transcriptional changes in the choroid plexus in AD to serve as a tool for future discovery.

This proposal is innovative by focusing on the role of the choroid plexus in Alzheimer’s disease and exploring whether activation of the renin-angiotensin system in the choroid plexus contributes to pathology. The choroid plexus is emerging as a key region of the brain important during Alzheimer’s disease, in particular for its role in cerebrospinal fluid production and immune surveillance. Our studies addressing the impact of the brain renin angiotensin system on disease progression will contribute to our understanding of how cardiovascular disease affects cognition.

The influence of the renin-angiotensin system on Alzheimer’s disease remains poorly understood despite the broad use of pharmacological therapeutics targeting this system to manage hypertension and cardiovascular disease. Thus, understanding how the renin-angiotensin system is modulated in the choroid plexus and its impact on Alzheimer’s disease may have important therapeutic implications for aging populations. The transcriptomic atlas of the choroid plexus in two mouse models will be a useful tool for the field, facilitating future investigation and identification of novel molecular targets.