# Hippocampal neurogenesis in cognitive function and dysfunction in Alzheimer's disease.

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2023 · $716,493

## Abstract

Abstract
In contrast to rodents, little is known about neurogenesis in the human brain. The few studies that examined
neurogenesis in the human hippocampus have come to vastly different conclusions. Determining the existence
and course of hippocampal neurogenesis in the human brain is critical for the understanding of brain function,
cognition, putative preventative and therapeutic approaches for the treatment of cognitive decline, Alzheimer’s
disease (AD) and related dementia (ADRD). Our previous studies showed that hippocampal neurogenesis
persists throughout the 10th decade of life. New neurons were observed in the brains of participants with no
cognitive impairments (NCI), as well as in patients exhibiting mild cognitive impairments (MCI) or AD.
Interestingly, the number of new neurons was significantly lower in MCI and AD compared to NCI. On the
other hand, the number of early differentiating and mature astrocytes was increased in the AD brain.
Importantly, higher numbers of neuroblasts were associated with better cognitive performance in the brains of
aging, MCI and AD patients. Intriguingly, levels of neurogenesis in the brains of SuperAgers, individuals in their
80ies who exhibit memory performance comparable to people in their 50ies, were significantly greater,
compared to age-matched individuals with age-appropriate cognitive function. Nevertheless, the observations
above were made using the same neurogenic proxies used in the rodent brain and the nature of cells in the
human brain recognized by these proxies is not clear. Evidently, studies that could not detect neurogenesis in
the human brain used the same proxies. Thus, the goal of this project is to test the hypothesis that hippocampal
neurogenesis persists in the aged and AD human brain and its level is associated with cognitive function. By
providing new evidence for the presence of hippocampal neurogenesis using novel tools that would validate
previously used proxies. Experiments in Aim 1 will examine the hypothesis that neural progenitor cells have a
lower level of proliferation and preferable differentiation into astrocytes leading to fewer new neurons in MCI and AD,
using multiplex RNA scope and neurogenic proxies. Experiments in Aim 2 will determine the spatial
organization of hippocampal neurogenesis in NCI, MCI and AD, and examine the hypothesis that autonomous
and non-autonomous factors in the DG determine the level of human neurogenesis in the aging and AD brain, using a
combination of spatial transcriptomics (pciSeq) and RNAseq. Aim 3 will address whether new neurons play a
role in cognitive reserve and resilience to AD. Experiments will examine the association between cognitive
performance , hippocampal neurogenesis and AD hallmarks in SuperAgers, age-appropriate cognitive
performance, MCI and AD patients. In summary, this project will provide novel crucial information about the
presence of neurogenesis and its role in hippocampal function in the human aging and AD brai...

## Key facts

- **NIH application ID:** 10619006
- **Project number:** 5R01AG076940-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Orly Lazarov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $716,493
- **Award type:** 5
- **Project period:** 2022-05-15 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10619006

## Citation

> US National Institutes of Health, RePORTER application 10619006, Hippocampal neurogenesis in cognitive function and dysfunction in Alzheimer's disease. (5R01AG076940-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10619006. Licensed CC0.

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