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

Abstract

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.

Transcriptomic Analysis of the Neurogenesis Signature suggests Continued but Minimal Neurogenesis in the Adult Human Hippocampus

“…Moreno-Jiménez et al, 2019 using tightly controlled conditions and state-of-the-art tissue processing methods, identified thousands of immature neurons, exhibiting variable degrees of maturation along differentiation stages, in DG of the neurologically healthy human subjects up to the ninth decade of life. They additionally found that continued neurogenesis was reduced in DG of Alzheimer's patients (8). Tobin et al, 2019 found AHN to persistent through the tenth decade of life and being detectable in patients with mild cognitive impairments and Alzheimer's disease.…”

“…Studies with contrasting evidence have emerged since then which ranged from absolute denial (3)(4)(5) to approval for the persistence of AHN even in old individuals (6)(7)(8). In adult mammals (including human) neurogenesis is thought to persist in the subgranular zone (SGZ) of the dentate gyrus (DG) region of the hippocampus (9).…”

“…More recently, more robust evidence emerged for AHN in humans (7,8). Moreno-Jiménez et al, 2019 using tightly controlled conditions and state-of-the-art tissue processing methods, identified thousands of immature neurons, exhibiting variable degrees of maturation along differentiation stages, in DG of the neurologically healthy human subjects up to the ninth decade of life.…”

Approach‐oriented coping strategy level may be related to volume of the whole hippocampus in the elderly

“…Further, neurogenesis confers resilience to chronic stress by inhibiting the activity of mature granule cells in the ventral DG . Notably, hippocampal neurogenesis in the DG also persists into old age . These findings suggest that approach‐oriented coping strategies may suppress atrophy and promote neurogenesis in the hippocampi of elderly persons who maintain their ADL and cognitive function.…”

Selective activation of estrogen receptors α and β: Implications for depressive-like phenotypes in female mice exposed to chronic unpredictable stress

“…The hippocampus retains the ability to produce new neurons in adulthood in a variety of species including humans (Kempermann et al, 2018;Moreno-Jiménez et al, 2019;Tobin et al, 2019). Adult hippocampal neurogenesis is reduced by chronic stress, promotes stress resilience, and is implicated in affective function and hypothalamic-pituitary-adrenal (HPA) axis regulation (Anacker et al, 2018;Schoenfeld and Gould, 2012;Surget et al, 2011), although most of this evidence is derived from male rodents.…”