Neurogenesis: A Key to Cognitive Resilience in Aging and Alzheimer’s Disease

Studies have confirmed the existence of neurogenesis – the birth of new neurons – in the adult human brain, but whether these newborn neurons bolster cognitive abilities has remained a topic of debate. Recent research led by Dr. Orly Lazarov at the University of Illinois, Chicago, suggests they do. A study published in Nature on February 25, 2026, linked the rate of neurogenesis to cognitive function, revealing that neurogenesis diminishes in Alzheimer’s disease (AD) while flourishing in “superagers” – older adults with exceptional memory. These changes are driven by epigenetic alterations that either suppress or enhance gene networks controlling cell differentiation.

Epigenetics and Neurogenesis: Distinct Changes in Aging and Disease

The research highlights the role of epigenetics in regulating neurogenesis, with distinct changes observed in aging and disease. Notably, the epigenetic profile in superagers doesn’t mirror that of young adults, suggesting it’s a response to aging rather than a simple delay of the aging process.

Neurogenesis Declines in Alzheimer’s, Increases in “Superagers”

Researchers found that neurogenesis wanes in AD, while it revs up in superagers. In superagers, new neurons exhibit a unique epigenetic profile indicative of resilience. This suggests that cognitive decline with age isn’t inevitable and that understanding the brains of those who maintain cognitive function could lead to preventative strategies.

Study Details and Methodology

Dr. Lazarov and her team characterized neurogenesis by analyzing gene expression and epigenetic changes in postmortem hippocampi from five cohorts: young adults, healthy older adults, individuals with preclinical AD, those with AD dementia, and superagers. They used single-nucleus RNA-Seq and single-nucleus assay for transposase-accessible chromatin with sequencing (ATAC-Seq) to define stages of neurogenesis and identify areas of the genome regulating gene expression.

The analysis delineated three distinct stages of neurogenesis: neural stem cells (NSCs), neuroblasts, and immature granule neurons. Surprisingly, differences between the cohorts were primarily driven by changes in active chromatin, rather than gene expression itself. The AD and superaging cohorts displayed almost opposite epigenetic profiles.

Key Findings

• Chromatin Changes Predominate: The study found that epigenetic changes, particularly in chromatin structure, are more significant than changes in gene expression during neurogenesis.
• NSC Abundance in AD: Individuals with AD showed an abundance of NSCs, but a scarcity of neuroblasts and immature neurons.
• Enhanced Neurogenesis in Superagers: Superagers had approximately double the amount of immature neurons compared to other cohorts, indicating more active neurogenesis.
• Resilience Networks: Superagers exhibited distinct epigenetic signatures, activating protective genes associated with cognitive resilience.
• Role of Astrocytes and CA1 Neurons: Epigenetic changes in astrocytes and gene expression in CA1 neurons were closely linked to healthy neurogenesis.

Implications for Alzheimer’s Disease Treatment

The findings suggest that activating resident adult neural stem cells to generate more immature neurons could be a potential therapeutic strategy for AD. Preservation of excitatory synapse integrity is also highlighted as a potential intervention target.

Expert Commentary

Other researchers in the field have lauded the study’s findings. Ryan Castro, Se Hoon Choi, and Rudolph Tanzi at Massachusetts General Hospital called the study a substantial advancement in understanding adult hippocampal neurogenesis. Gerd Kempermann at the Center for Regenerative Therapies in Dresden, Germany, supported the idea of a “neurogenic reserve” that boosts cognition, suggesting new neurons may compensate for age- or disease-related losses in the hippocampus.

Further Research

Dr. Lazarov’s team plans to further investigate the functional effects of the identified resilience gene networks in cultured stem cells. They also aim to understand how astrocytes and CA1 neurons influence the neurogenic niche.

Sources

Orly Lazarov, PhD – University of Illinois Chicago

Orly Lazarov, PhD – Center for CardioVascular Research

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