{"doi":"10.1016/j.stemcr.2021.05.006","title":"Questioning the evidence for a Janus-faced nature of adult neurogenesis in Alzheimer’s disease","abstract":"A substantial number of studies support the notion that hippocampal neurogenesis is deficient in mouse models of Familial Alzheimer’s disease (FAD) as well as in Alzheimer’s disease (AD) patients (Disouky and Lazarov, 2021Disouky A. Lazarov O. Adult hippocampal neurogenesis in Alzheimer’s disease.Prog. Mol. Biol. Transl. Sci. 2021; 177: 137-156Crossref PubMed Scopus (7) Google Scholar). In agreement with that, interventions that upregulate neurogenesis have led to the attenuation of pathology and rescue of memory impairments (see for example Choi et al., 2018Choi S.H. Bylykbashi E. Chatila Z.K. Lee S.W. Pulli B. Clemenson G.D. Kim E. Rompala A. Oram M.K. Asselin C. et al.Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model.Science. 2018; 361: eaan8821Crossref PubMed Scopus (324) Google Scholar). Likewise, previous studies have showed that ablating neurogenesis in FAD mice exacerbated learning and memory (Choi et al., 2018Choi S.H. Bylykbashi E. Chatila Z.K. Lee S.W. Pulli B. Clemenson G.D. Kim E. Rompala A. Oram M.K. Asselin C. et al.Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model.Science. 2018; 361: eaan8821Crossref PubMed Scopus (324) Google Scholar; Hollands et al., 2017Hollands C. Tobin M.K. Hsu M. Musaraca K. Yu T.S. Mishra R. Kernie S.G. Lazarov O. Depletion of adult neurogenesis exacerbates cognitive deficits in Alzheimer’s disease by compromising hippocampal inhibition.Mol. Neurodegener. 2017; 12: 64Crossref PubMed Scopus (69) Google Scholar). In contrast, a recent study by Zhang et al. suggests that ablating neurogenesis improves synaptic and cognitive function in FAD mice (Zhang et al., 2021Zhang X. Mei Y. He Y. Wang D. Wang J. Wei X. Yang E. Zhou D. Shen H. Peng G. et al.Ablating Adult Neural Stem Cells Improves Synaptic and Cognitive Functions in Alzheimer Models.Stem Cell Reports. 2021; 16: 89-105Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar). Upon closer examination of the experimental approach, we raise questions concerning the study design and the authors’ interpretation of the results, and thus, reveal critical differences between this study and the existing body of literature (see for example [Choi et al., 2018Choi S.H. Bylykbashi E. Chatila Z.K. Lee S.W. Pulli B. Clemenson G.D. Kim E. Rompala A. Oram M.K. Asselin C. et al.Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model.Science. 2018; 361: eaan8821Crossref PubMed Scopus (324) Google Scholar; Hollands et al., 2017Hollands C. Tobin M.K. Hsu M. Musaraca K. Yu T.S. Mishra R. Kernie S.G. Lazarov O. Depletion of adult neurogenesis exacerbates cognitive deficits in Alzheimer’s disease by compromising hippocampal inhibition.Mol. Neurodegener. 2017; 12: 64Crossref PubMed Scopus (69) Google Scholar]). To deplete neurogenesis in APPswe/PS1ΔE9, the authors bred this FAD line with mice expressing glial fibrillary acidic protein-driven thymidine kinase (GFAP-TK). These mice were then treated with valganciclovir to indiscriminately deplete all proliferating GFAP+ cells. It is essential to note that neural stem cells (NSCs) comprise only a small portion of all GFAP+ cells with the majority of GFAP expression found in astrocytes (Kriegstein and Alvarez-Buylla, 2009Kriegstein A. Alvarez-Buylla A. The glial nature of embryonic and adult neural stem cells.Annu. Rev. Neurosci. 2009; 32: 149-184Crossref PubMed Scopus (1568) Google Scholar). In a second approach, the authors used systemic treatment with methylazoxymethanol acetate (MAM) for the depletion of neurogenesis. Similarly to the first approach, the choice of ablating neurogenesis by this treatment suffers from lack of specificity. This approach ablates dividing cells and may include the abolishment of astrocytes, microglia, neural progenitor cells, and others. In addition, MAM could alter the composition of the gut microbiota, decrease microbes,","journal":"Stem Cell Reports","year":2021,"id":211117,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":800019,"name":"Muskan Gupta","orcid":"0000-0002-6668-6354","position":1,"is_corresponding":false},{"id":728632,"name":"Rachana Mishra","orcid":"0000-0003-2572-9570","position":2,"is_corresponding":false},{"id":785915,"name":"Pavan Kumar","orcid":"0000-0003-3099-1477","position":3,"is_corresponding":false},{"id":800020,"name":"Ahmed Disouky","orcid":"0000-0001-9055-8830","position":4,"is_corresponding":false},{"id":462544,"name":"Terilyn K. L. Stephen","orcid":null,"position":5,"is_corresponding":false},{"id":800566,"name":"Karen Rakowiecki","orcid":null,"position":6,"is_corresponding":false},{"id":461402,"name":"Orly Lazarov","orcid":"0000-0002-5887-948X","position":7,"is_corresponding":false},{"id":800018,"name":"Trongha Phan","orcid":"0000-0003-4736-9705","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-18T23:52:16.049481Z","pmid":"34048691","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}