A new study published on 25 March in Nature provides “clear and definitive evidence” that neurogenesis ― the process used by the brain to make new cells or neurons ― continues throughout life (1). However, the findings also showed that the number of new neurons is severely reduced in the brains of people with Alzheimer’s disease, regardless of age.
Scientists have long hoped neurogenesis could be used to help treat diseases like Alzheimer’s. However, the question of whether older brains can make new neurons has remained a topic of debate for many years now. Some scientists believe new brains cells are made well into old age, whereas others argue that humans are no longer capable of producing neurons in adulthood.
In fact, one study published in Nature last year completely contradicted previous works, reporting that the generation of newborn neurons gradually dwindles with age before coming to a complete stop in adolescence (2).
The contradictions among previous findings are mainly owing to the differences in the testing and tissue processing methods used in the studies. Brain tissue is normally preserved with using a fixative called paraformaldehyde, for months or years. This can damage brain cells and prevent the fluorescent marker ― the doublecortin (DCX) protein ― used to detect new brain cells from binding to them.
The team of Spanish scientists found that the number of cells testing positive for the DCX biomarker declines dramatically in brain tissue after just 48 hours in the fixative. So, to overcome this, they used tightly controlled conditions and state-of-the-art tissue processing methods, and a fixation time of only 24 hours.
The researchers examined the brain tissue of 13 individuals with healthy brains before death, aged 43 to 87, and discovered that new cells are indeed formed in the adult brain. Newborn neurons were found in the area of the brain called the dentate gyrus of the hippocampus ― the area of the brain plays a crucial role in learning, memory, mood, and emotion. However, the authors also report that the numbers of newborn brain cells declined steadily with age.
Furthermore, the hippocampus is one of the brain regions most affected in Alzheimer’s, according to the authors, which is why they also decided to study the brains of 45 people aged 52 to 97 diagnosed with the disease before they died.
Although all the individuals showed evidence of new brain cells, there were distinct differences in the number of these newborn cells. Healthy brains had 50 to 75 per cent more new cells compared to the brains of Alzheimer’s patients and the number of new cells progressively declined as the disease advanced.
Around 50 million people suffer from dementia and Alzheimer’s around the world. The authors suggest that non-invasive techniques to detect newly-formed brain cells could one day help diagnose Alzheimer’s much earlier. Early detection may provide the opportunity for interventions that could either slow down or even halt the disease from progressing further.
Moreover, the findings suggest therapeutic strategies could potentially focus on increasing the number of new neurons to prevent or slow down the progression of the disease.
(1) Moreno-Jiménez, E.P. et al.Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nature (2019). DOI: 10.1038/s41591-019-0375-9
(2) Sorrells, S.F. et al. Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature (2018). DOI: 10.1038/nature25975