This is a very strong claim and there are other papers/evidence that both support and contradict this finding. For example, Sorrells et al., 2018 (Nature) claimed that AHN drops sharply in childhood and becomes nearly undetectable in adults. However, Boldrini et al., 2018 (Cell Stem Cell) examined hippocampal tissue from adults 14–79 years old and found stable numbers of immature neurons across ages. I think this is particulatly interesting to see the same journal (Nature) publish two papers that have contradicting findings...

[Sorrells SF, Paredes MF, Cebrian-Silla A, Sandoval K, Qi D, Kelley KW, James D, Mayer S, Chang J, Auguste KI, Chang EF, Gutierrez AJ, Kriegstein AR, Mathern GW, Oldham MC, Huang EJ, Garcia-Verdugo JM, Yang Z, Alvarez-Buylla A. Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature. 2018 Mar 15;555(7696):377-381. doi: 10.1038/nature25975. Epub 2018 Mar 7. PMID: 29513649; PMCID: PMC6179355. https://pubmed.ncbi.nlm.nih.gov/29513649/

Boldrini M, Fulmore CA, Tartt AN, Simeon LR, Pavlova I, Poposka V, Rosoklija GB, Stankov A, Arango V, Dwork AJ, Hen R, Mann JJ. Human Hippocampal Neurogenesis Persists throughout Aging. Cell Stem Cell. 2018 Apr 5;22(4):589-599.e5. doi: 10.1016/j.stem.2018.03.015. PMID: 29625071; PMCID: PMC5957089. https://pmc.ncbi.nlm.nih.gov/articles/PMC5957089/

In my opinion, this is a huge strength of the paper and methodology of this experiment. They could have easily done this research with one antibody and produced valid results.

This may not be possible but it would be interesting to see if using brains of living humans instead of post-mortem brains...It is a stretch though.

I think this is a weakness of the paper - yes, the researchers measured the presence of DCX+ cells but didn't show or look into whether the cells were integrate into circuitry which would be incredibly important to know in order to use these findings to create an intervention for neurogenesis.

General / Study Terms

AHN – Adult Hippocampal Neurogenesis

AD – Alzheimer’s Disease

PMD – Post-Mortem Delay

DG – Dentate Gyrus

DGC – Dentate Granule Cell

GCL – Granule Cell Layer

ML – Molecular Layer

SGZ – Subgranular Zone

H – Hilus

EC – Entorhinal Cortex

CA1, CA3 – Cornu Ammonis hippocampal subfields

Pyr – Pyramidal layer

Cell Markers & Proteins

DCX – Doublecortin (marker of immature neurons)

Prox1 – Prospero Homeobox 1 (granule cell fate marker)

PSA-NCAM – Polysialic Acid–Neural Cell Adhesion Molecule (immature neuron marker)

CR – Calretinin (calcium-binding protein; early immature neuron marker)

CB – Calbindin (calcium-binding protein; marker of more mature neurons)

NeuN – Neuronal Nuclei (marker of mature neurons)

βIII-tubulin – Cytoskeletal protein (neuronal identity marker)

Tau (pTau) – Microtubule-associated protein; phosphorylated tau linked to AD pathology

β-amyloid (Aβ) – Amyloid-beta peptide, forms plaques in AD

Methods & Technical

NaBH₄ – Sodium borohydride (used in tissue treatment)

HC-AR – Heat and Chemical Antigen Retrieval (histological technique)

CI – Confidence Interval

ANOVA – Analysis of Variance (statistical test)

s.e.m. – Standard Error of the Mean

I think this conclusion is a bit abrupt and doesn't address practical ways these findings could be used as interventions that could realistically enhance neurogenesis. What would these interventions look like? Stem cell therapies, small molecules, or lifestyle interventions? Morphological heterogeneity of DCX+ cells suggests a long maturation timeline in humans. Could this slower timescale mean interventions to boost AHN might require years to show benefits?

Does this imply neurogenesis decline is a cause or a consequence of AD pathology?

Previous failures to detect AHN might reflect differences in tissue handling. What are the implications for studies relying on brain bank samples with variable fixation? Aka - what really made this brain bank different?

Why is the dentate gyrus uniquely suited for ongoing neurogenesis compared to other brain regions? Could there be evolutionary reasons for maintaining this capacity?