Investigating the contribution of the long non-coding RNA (lncRNA) Neat1 to memory deficits associated with normal aging and Alzheimer’s disease (AD).

Aging and AD are associated with profoundly altered gene expression profiles in the hippocampus; yet cell-type specific transcriptional changes underlying memory impairment are not well understood. The lncRNA Neat1 is increased in a highly cell-type dependent manner in the brain during normal aging and in AD. We previously demonstrated that during normal aging, a pancellular increase Neat1 drives repression of memory-critical genes while reducing Neat1 in dCA1 of the hippocampus is sufficient to improve hippocampus-dependent memory in aged mice. We hypothesized that cell-type specific changes in Neat1 contribute to age and AD-related changes in gene expression and subsequent memory impairment.

These findings suggest the human APP transgene introduces an accelerated aging state in hippocampal astrocytes which then contributes to memory impairment. This study addresses an urgent need to understand cell-type specific mechanisms contributing to memory dysfunction in aging and AD.