New neurons keep developing in the human brain until at least our 90s

The number of new neurons could one day serve as a biomarker for Alzheimer’s disease progression.

New neurons continue to develop in the human brain up until the age of 90, a new Nature Medicine study has found. Researchers analyzed tissue samples from 58 participants and found that, although age does slow development, adults continue to develop new neurons – called adult neurogenesis – in the hippocampus. However, people suffering from Alzheimer’s disease showed a sharp decrease in the development of new neurons. Researchers hope that finding a non-invasive way to detect the number of new immature neurons in living individuals could one day be used as a biomarker for Alzheimer’s disease progression.

We spoke to author Maria Llorens-Martín about the work.

ResearchGate: What motivated this study?

Maria Llorens-Martín: We wanted to study adult hippocampal neurogenesis – the development of new neurons in the hippocampus – in humans as they age. In particular, we wanted to understand the different stages of the process and how they were altered in Alzheimer´s disease (AD) patients.

RG: Can you tell us briefly what you discovered?

Llorens-Martín: We found that new neurons develop in our dentate gyrus – a part of the hippocampus – at least until we are in our 90s. Also, that certain methodologies are critical to be able to detect the markers of adult hippocampal neurogenesis in the human brain. And that adult hippocampal neurogenesis is dramatically impaired in AD patients.

RG: What does the ability to develop new neurons do for us as we age?

Llorens-Martín: Studies in mice have revealed that newborn neurons in the dentate gyrus are crucial for processing certain types of memory. The generation of new neurons greatly increases the plasticity of the hippocampal circuit. Moreover, specifically during aging, newly generated neurons contribute to the so-called neurogenic reserve. In other words, it means that they constitute a kind of reserve of plasticity that our brains can use at advanced ages.

RG: Where did the belief that older adults don’t develop new neurons come from?

Llorens-Martín: As far as we know, most of the neurons present in our brains do not undergo regeneration during our lifetime. Thus, the hippocampus is one of the few exceptions. This has been clearly demonstrated in rodents and other species of mammals. Previous reports indicated that the process also occurred in humans. However, a paper last year reported that the authors failed to detect markers of immature neurons in the adult human hippocampus.

RG: Why do you think their results differed to yours?

Llorens-Martín: Our study shows that methodology is critical in showing neurogenesis in human hippocampal tissue. By using the same brain samples but processed in different ways we found that neurogenesis is either abundant, rare, or it does not exist at all. But the cells are there; it is just that we were unable to detect them.

RG: Can you describe the conditions that can prevent the brain from developing new neurons?

Llorens-Martín: It has been demonstrated that only some so-called permissive environments are suitable for the generation of new neurons in adult brains. These environments have very specific characteristics (special vasculature, glial cells, extracellular matrix, etc.). I believe there is a need, in some areas of the brain, for principal neurons to be stable in terms of cell replacement. Although we still have so much to learn about where and how the memory is “physically stored” in our brains. In my personal opinion, it is possible that different forms of plasticity, either the generation of new neurons (as it occurs in the dentate gyrus) or the remodeling of synaptic connections (that occurs in most of brain areas) contribute differently to memory storage, and all these phenomena are probably required for a proper memory storage.

RG: What do your findings mean for our understanding of Alzheimer's?

Llorens-Martín: Our results demonstrate that adult neurogenesis drops remarkably at early stages of the disease, even before the dentate gyrus is altered by the presence of Amyloid Beta and Phosphorylated Tau. Thus, if we could detect the levels of adult neurogenesis in living individuals by non-invasive methods, this decrease might turn into a relevant biomarker of the disease progression. Moreover, if these neurons are actually important for memory processing in human beings, and we could reverse the decrease that takes place at these initial stages, we may prevent or slow down some aspects of the reduced neural plasticity observed in AD patients.

RG: What can people do to help with your research?

Llorens-Martín: Yes, I would like to emphasize that this work has been possible thanks to the generosity of donors and families. And I would like to remark how important it is to donate our brains; this is, by now, one of the few ways researchers can investigate how the human brain works. It doesn’t matter if we are neurologically healthy or not, our brains are really important for research. They are a treasure indeed.

Image credit djneight.