scRNAseq + scV(D)J of cerebrospinal fluid samples across age

Cerebrospinal fluid (CSF) contains a tightly regulated, specialized immune system. Yet, little is known about how aging influences CSF immunity in cognitively typical versus cognitively impaired individuals. Here, we performed single cell RNA sequencing (scRNAseq) on CSF collected from 45 cognitively typical subjects ranging from 54-82 years old. We then assessed age-related transcriptomic changes using several bioinformatic approaches, including linear and local polynomial regression. We reveal pronounced changes to several CSF immune cell types that occur around age 75, including alterations to clonally expanded T cells and activated monocytes. We then compared CSF immune systems from cognitively typical subjects to 14 subjects with mild cognitive impairment or Alzheimer's disease. Our results indicate disparate age-related CSF immune system perturbations in cognitively impaired subjects. These results highlight the potential to utilize CSF immune changes to identify age-related neuroinflammation in cognitively impaired individuals. Overall design: Examination of immune changes in the CSF due to aging and MCI/AD