Association of adult hippocampal neurogenesis with alzheimer’s disease

Atryee Gope


Neurogenesis in the adult brain has been reported to occur within three distinct regions, of which Hippocampus is the most studied one because of its importance in cognition and memory. Alzheimer’s disease attributes to almost 62% of all dementia cases. A recent study has established a link between adult hippocampal neurogenesis and alzheimer’s disease wherein a sharp decline in AHN is observed in patients suffering from alzheimer’s. This review summarizes alzheimer’s disease, the decline in AHN in alzheimer’s patients and probes into the efficacy of the newly generated hippocampal neurons in the context of memory and cognition. It also discusses the potential of targeting reduced AHN in alzheimer’s patients using neural stem cell-based therapy.


Dementia, Alzheimer’s disease, Neurogenesis, Adult hippocampal neurogenesis, Neural stem cells, Stem cell-based therapy

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Hugo J, Ganguli M. Dementia and cognitive impairment: epidemiology, diagnosis, and treatment. Clin Geriatr Med. 2014;30(3):421-42.

Poon LW, Woodard JL, Stephen ML, Green R, Gearing M, Davey A, et al. Understanding dementia prevalence among centenarians. J Gerontol A Biol Sci Med Sci. 2012;67(4):358-65.

Qiu C, Fratiglioni L. Aging without dementia is achievable: current evidence from epidemiological research. J Alzheimers Dis. 2018;62(3):933-42.

Lanctôt KL, Amatniek J, Ancoli-Israel S, Arnold SE, Ballard C, Cohen-Mansfield J, et al. Neuropsychiatric signs and symptoms of Alzheimer’s disease: New treatment paradigms. Alzheimers Dement Transl Res Clin Interv. 2017;3 (3):440-9.

Bature F, Guinn B, Pang D, Pappas Y. Signs and symptoms preceding the diagnosis of Alzheimer’s disease: a systematic scoping review of literature from 1937 to 2016. BMJ Open. 2017;7(8):e015746.

Benoit M, Dygai I, Migneco O, Robert PH, Bertogliati C, Darcourt J, et al. Behavioral and Psychological symptoms in Alzheimer’s Disease. Dement Geriatr Cogn Disord. 1999;10(6):511-7.

Zagorski N. Researchers continue to debate adult neurogenesis. Available at: Accessed on 20 August 2020.

Ming G-L, Song H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron. 2011;70(4):687-702.

Moreno-Jiménez P, Flor-García M, Terreros-Roncal J, Rábano A, Cafini F, Pallas-Bazarra N, et al. Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Available at: Accessed on 20 August 2020.

Bao H, Song J. Treating brain disorders by targeting adult neural stem cells. Trends Mol Med. 2018; 24(12): 991-1006.

MacGill M. Alzheimer’s disease: Symptoms, stages, causes, and treatment. Available at: Accessed on 20 August 2020.

Robert E, Patrick K, Christian H, Christoph T, Kai S. Amyloidogenic processing of the Alzheimer β-amyloid precursor protein depends on lipid rafts . Available at: 113.long. Accessed on 20 August 2020.

Boutajangout A, Sigurdsson EM, Krishnamurthy PK. Tau as a therapeutic target for alzheimer’s disease. Curr Alzheimer Res. 2011;8(6):666-77.

Johnson GVW, Stoothoff WH. Tau phosphorylation in neuronal cell function and dysfunction. J Cell Sci. 2004;117(Pt 24):5721-9.

Types of alzheimer’s disease. Available at: Accessed on 20 August 2020.

Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science. 1993;261(5123):921-3.

Dose J, Huebbe P, Nebel A, Rimbach G. APOE genotype and stress response - a mini review. Lipids Health Dis. 2016;15:121.

Mendiola-Precoma J, Berumen LC, Padilla K, Garcia-Alcocer G. Therapies for prevention and treatment of alzheimer's disease. Biomed Res Int. 2016;2016:2589276.

Maliszewska-Cyna E, Lynch M, Oore JJ, Nagy PM, Aubert I. The Benefits of exercise and metabolic interventions for the prevention and early treatment of alzheimer’s disease. Curr Alzheimer Res. 2017;14 (1):47-60.

Chieffi S, Messina G, Villano I, Messina A, Esposito M, Monda V, et al. Exercise influence on hippocampal function: possible involvement of Orexin-A. Front. Physiol. 2017;8:85.

Ma C-L, Ma X-T, Wang J-J, Liu H, Chen Y-F, Yang Y. Physical exercise induces hippocampal neurogenesis and prevents cognitive decline. Behav Brain Res. 2017;317:332-9.

Jessberger S. Neural repair in the adult brain. Faculty Rev. 2016;5:F1000.

Lois C, Kelsch W. Adult neurogenesis and its promise as a hope for brain repair. Front Neurosci. 2014;8:165.

Pedro B, José PA. Adult hippocampal neurogenesis: regulation and possible functional and clinical correlates. Front. Neuroanat.2018;52(8):213-9.

Bernier PJ, Bédard A, Vinet J, Lévesque M, Parent A. Newly generated neurons in the amygdala and adjoining cortex of adult primates. Proc Natl Acad Sci. 2002;99(17):11464-9.

Fowler CD, Liu Y, Wang Z. Estrogen and adult neurogenesis in the amygdala and hypothalamus. Brain Res Rev. 2008;57(2):342-51.

Anand KS, Dhikav V. Hippocampus in health and disease: An overview. Ann Indian Acad Neurol. 2012;15(4):239-46.

Toda T, Parylak SL, Linker SB. The role of adult hippocampal neurogenesis in brain health and diseases. Mol Psychiatry. 2019;24:67-87.

Schoenfeld TJ, Cameron HA. Adult neurogenesis and mental illness. Neuropsychopharmacol. 2015;40 (1):113-28.

Yun S, Reynolds RP, Masiulis I, Eisch AJ. Re-evaluating the link between neuropsychiatric disorders and dysregulated adult neurogenesis. Nat Med. 2016;22(11):1239-47.

Steiner E, Tata M, Frisén JA. Fresh look at adult neurogenesis. Nat Med. 2019;25:542-3.

Peng L, Bonaguidi MA. Function and dysfunction of adult hippocampal neurogenesis in regeneration and disease. Am J Pathol. 2018;188(1):23-8.

Mu Y, Gage FH. Adult hippocampal neurogenesis and its role in Alzheimer’s disease. Mol Neurodegener. 2011;6:85.

More evidence that humans do appear to create new neurons in old age. Available at: Accessed on 20 August 2020.

Jessberger S. Stem cell-mediated regeneration of the adult brain. Transfus Med Hemother. 2016;43(5): 321-6.

Duncan T, Valenzuela M. Alzheimer’s disease, dementia, and stem cell therapy. Stem Cell Res Ther. 2017;8(1):111.

Bali P, Lahiri DK, Banik A, Nehru B, Anand A. Potential for stem cells therapy in alzheimer’s disease: do neurotrophic factors play critical role? Curr Alzheimer Res. 2017;14(2):208-20.

Kwak K-A, Lee S-P, Yang J-Y, Park Y-S. Current perspectives regarding stem cell-based therapy for alzheimer’s disease. Stem Cells Int. 2018; 2018: 6392986.

Choi SH, Bylykbashi E, Chatila ZK, Lee SW, Pulli B, Clemenson GD, et al. Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model. Science. 2018;361(6406):eaan8821.

Bergmann O, Spalding KL, Frisén J. Adult Neurogenesis in Humans. Cold Spring Harb Perspect Biol. 2015;7(7):a018994.

Duncan T, Valenzuela M. Alzheimer’s disease, dementia, and stem cell therapy. Stem Cell Res Ther. 2017;8(1):111.

Gandhi S, Gupta J, Tripathi PP. The curious case of human hippocampal neurogenesis. ACS Chem Neurosci. 2019;10(3):1131-2.