Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer's disease

The hippocampus is one of the most affected areas in Alzheimer's disease (AD) . Moreover, this structure hosts one of the most unique phenomena of the adult mammalian brain, namely, the addition of new neurons throughout life . This process, called adult hippocampal neurogenesis (AHN), confers...

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Vydáno v:Nature medicine Ročník 25; číslo 4; s. 554 - 560
Hlavní autoři: Moreno-Jiménez, Elena P, Flor-García, Miguel, Terreros-Roncal, Julia, Rábano, Alberto, Cafini, Fabio, Pallas-Bazarra, Noemí, Ávila, Jesús, Llorens-Martín, María
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Nature Publishing Group 01.04.2019
Témata:
Adult
Aging
Alzheimer Disease - pathology
Alzheimer's disease
Biomarkers - metabolism
Brain
Cell Differentiation
Controlled conditions
Dentate gyrus
Dentate Gyrus - pathology
Doublecortin Domain Proteins
Hippocampal plasticity
Hippocampus
Hippocampus - pathology
Humans
Identification methods
Maturation
Microtubule-Associated Proteins - metabolism
Neurogenesis
Neurons
Neuropeptides - metabolism
Physiology
ISSN:1078-8956, 1546-170X, 1546-170X
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Shrnutí:The hippocampus is one of the most affected areas in Alzheimer's disease (AD) . Moreover, this structure hosts one of the most unique phenomena of the adult mammalian brain, namely, the addition of new neurons throughout life . This process, called adult hippocampal neurogenesis (AHN), confers an unparalleled degree of plasticity to the entire hippocampal circuitry . 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.
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ISSN:1078-8956
1546-170X
1546-170X
DOI:10.1038/s41591-019-0375-9