Human Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer’s Disease Patients

Highlights

• Neurogenic subpopulations are evenly distributed along the dorsal-ventral hippocampal axis

• Numbers of neuroblasts are reduced in MCI

• Higher numbers of DCX⁺PCNA⁺ cells correlate with higher cognitive scores

• Increased DCX⁺PCNA⁺ cells correlate with levels of interaction of presynaptic SNAREs

Summary

Whether hippocampal neurogenesis persists throughout life in the human brain is not fully resolved. Here, we demonstrate that hippocampal neurogenesis is persistent through the tenth decade of life and is detectable in patients with mild cognitive impairments and Alzheimer’s disease. In a cohort of 18 participants with a mean age of 90.6 years, Nestin⁺Sox2⁺ neural progenitor cells (NPCs) and DCX⁺ neuroblasts and immature neurons were detected, but their numbers greatly varied between participants. Nestin⁺ cells localize in the anterior hippocampus, and NPCs, neuroblasts, and immature neurons are evenly distributed along the anterior to posterior axis. The number of DCX⁺PCNA⁺ cells is reduced in mild cognitive impairments, and higher numbers of neuroblasts are associated with better cognitive status. The number of DCX⁺PCNA⁺ cells correlates with functional interactions between presynaptic SNARE proteins. Our results suggest that hippocampal neurogenesis persists in the aged and diseased human brain and that it is possibly associated with cognition.