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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE200164 | GEO | 2022/12/12

REPOSITORIES: GEO

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Project description:Aging is often associated with cognitive decline, but many elderly individuals maintain a high level of function throughout life. Here we studied outbred rats, which also exhibit individual differences across a spectrum of outcomes that includes both preserved and impaired spatial memory. Previous work in this model identified the CA3 subfield of the hippocampus as a region critically affected by age and integral to differing cognitive outcomes. Earlier microarray profiling revealed distinct gene expression profiles in the CA3 region, under basal conditions, for aged rats with intact memory and those with impairment. Because prominent age-related deficits within the CA3 occur during neural encoding of new information, here we used microarray analysis to gain a broad perspective of the aged CA3 transcriptome under activated conditions. Behaviorally induced CA3 expression profiles differentiated aged rats with intact memory from those with impaired memory. In the activated profile, we observed substantial numbers of genes (greater than 1000) exhibiting increased expression in aged unimpaired rats relative to aged impaired, including many involved in synaptic plasticity and memory mechanisms. This unimpaired aged profile also overlapped significantly with a learning induced gene profile previously acquired in young adults. Alongside the increased transcripts common to both young learning and aged rats with preserved memory, many transcripts behaviorally-activated in the current study had previously been identified as repressed in the aged unimpaired phenotype in basal expression. A further distinct feature of the activated profile of aged rats with intact memory is the increased expression of an ensemble of genes involved in inhibitory synapse function, which could control the phenotype of neural hyperexcitability found in the CA3 region of aged impaired rats. These data support the conclusion that aged subjects with preserved memory recruit adaptive mechanisms to retain tight control over excitability under both basal and activated conditions. RNA profiles from cognitively unimpaired and impaired aged rats were compared under 2 conditions: spatial learning task and a non-spatial learning task.

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

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