期刊
NATURE MEDICINE
卷 25, 期 4, 页码 554-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41591-019-0375-9
关键词
-
资金
- Spanish Ministry of Economy and Competitiveness [SAF-2017-82185-R, RYC-2015-171899, SAF-2014-53040-P]
- Alzheimer's Association [2015-NIRG-340709, AARG-17-528125]
- Association for Frontotemporal Degeneration
- Comunidad de Madrid [PEJD-2017-PRE/BMD-3439]
- Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED, Spain)
- Fundacion Ramon Areces
- Banco de Santander
- Universidad Autonoma de Madrid doctoral fellowship (FPI-UAM 2017 program)
The hippocampus is one of the most affected areas in Alzheimer's disease (AD)(1). Moreover, this structure hosts one of the most unique phenomena of the adult mammalian brain, namely, the addition of new neurons throughout life(2). This process, called adult hippocampal neurogenesis (AHN), confers an unparalleled degree of plasticity to the entire hippocampal circuitry(3,4). Nonetheless, direct evidence of AHN in humans has remained elusive. Thus, determining whether new neurons are continuously incorporated into the human dentate gyrus (DG) during physiological and pathological aging is a crucial question with outstanding therapeutic potential. By combining human brain samples obtained under tightly controlled conditions and state-of-the-art tissue processing methods, we identified thousands of immature neurons in the DG of neurologically healthy human subjects up to the ninth decade of life. These neurons exhibited variable degrees of maturation along differentiation stages of AHN. In sharp contrast, the number and maturation of these neurons progressively declined as AD advanced. These results demonstrate the persistence of AHN during both physiological and pathological aging in humans and provide evidence for impaired neurogenesis as a potentially relevant mechanism underlying memory deficits in AD that might be amenable to novel therapeutic strategies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据