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This study fills the gap with matched male and female brains, using optical fractionator and nucleator probes to quantify CA1 total neuron counts and mean neuron volumes across 22 hemispheres. CA1 neuron counts positively correlate with ex vivo MRI hippocampal volume. Insufficient evidence links age, sex, hemisphere, or mild p-tau pathology with CA1 neuron measures.",{"@graph":69,"@context":126},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/filling-in-the-gap-hippocampal-ca1-neuronal-counts-and-volumes-in-female-cognitive-controls/435033/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/filling-in-the-gap-hippocampal-ca1-neuronal-counts-and-volumes-in-female-cognitive-controls/435033.png","ImageObject",300,407,{"name":92,"@type":93},"Elsa","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does the study address about CA1 stereological research?","Question",{"text":112,"@type":113},"Previous CA1 stereological studies primarily used male samples, so female total neuron counts and neuron-size data were missing or underrepresented. The study targets this gap by providing baseline data in both sexes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were CA1 total neuron counts and neuron volumes measured?",{"text":117,"@type":113},"CA1 total neuron counts and mean neuron volumes were quantified using optical fractionator and nucleator probes across human brain hemispheres.",{"name":119,"@type":110,"acceptedAnswer":120},"What relationship did the study find between CA1 neuron counts and hippocampal volume?",{"text":121,"@type":113},"CA1 total neuron count showed a positive correlation with hippocampal volume measured from ex vivo MRI, supporting earlier findings.",{"name":123,"@type":110,"acceptedAnswer":124},"Did age, sex, hemisphere, or p-tau pathology show evidence of association with CA1 neuron measures?",{"text":125,"@type":113},"The study reports insufficient evidence for associations between age, sex, hemisphere, or mild p-tau pathology and CA1 total neuron count, mean neuron volume, and area.","https://schema.org",{"og:url":83,"og:type":128,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":130,"canonical":83},"index,follow",{"doc_id":132,"site_id":62},435033,1790817251,{"code":4,"msg":5,"data":135},{"doc_id":132,"user_id":136,"nickname":92,"user_avatar":137,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":143,"language":144,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":145,"faqs":146,"seo_title":147,"seo_description":67,"update_tm":148,"read_time":26,"preview_page_count":4},137455077381,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","Author Manuscript Author Manuscript Author Manuscript Author Manuscript  \n\n| | HHS Public Access\u003Cbr>Author manuscript\u003Cbr>Neurobiol Dis. Author manuscript; available in PMC 2026 January 05. |\n| --- | --- |\n\nPublished in final edited form as:  \nNeurobiol Dis. 2025 December ; 217: 107161. doi:10.1016/j.nbd.2025.107161 .  \nFilling in the gap: Hippocampal CA1 neuronal counts and volumes in female cognitive controls  \nErin-Marie C. Smitha, Anne M. Alexandera, Kaitlyn H. Watta, Emma W. Rosenbluma, Nicole Pihlstroma, Joshua L. Chasea, Nathaniel Mercaldoa,b, Elizabeth Connerc, André van der Kouwea,b, Matthew P. Froschb,c, Jean C. Augustinacka,b,*  \naAthinoula A. Martinos Center for Biomedical Imaging, Radiology, Massachusetts General Hospital, 149 13th St, Boston, MA 02129, USA  \nb Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA  \ncC.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA  \nAbstract  \nCA1 is a subfield in the human hippocampus that is particularly vulnerable to hypoxia. Previous stereological studies on CA1 have examined primarily male samples, leaving female total neuron counts not represented or underrepresented in total neuron count and neuron size studies. Our study sought to fill in the gap and provide baseline data on an equal number of male and female brains, representing both hemispheres with optimal stereology methods. Twenty-two human brain hemispheres, 11 females, 11 males (9 right hemispheres, 13 left hemispheres), were counted using the optical fractionator and nucleator probes for total neuron count and mean neuron volumes. Hippocampal volume was measured in a subset of 20 samples from 1 mm isotropic ex vivo MRI. The CA1 total neuron count across all samples was 5.01 × 106 ± 1.77 × 106 (median ± interquartile range) neurons. The CA1 neuron volume across all samples was  \n4461.9 ± 767.1 μm3 (median ± interquartile range) . Total neuron count was shown to positively correlate with hippocampal volume measured from ex vivo MRI, validating previous studies.  \nThere was insufficient evidence of associations between age, sex, hemisphere, or p-tau pathology in hippocampus (isolated to mild) and total neuron count, mean neuron volume, and area. This  \nThis is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)).  \n*Corresponding author at: Athinoula A. Martinos Center for Biomedical Imaging, Radiology, Massachusetts General Hospital, 149 13th St, Suite 2301, Boston, MA 02129, [USA. jaugustinack@mgh.harvard.edu](USA. jaugustinack@mgh.harvard.edu) (J.C. Augustinack) .  \nCRediT authorship contribution statement  \nErin-Marie C. Smith: Formal analysis, Investigation, Visualization, Writing – original draft, Writing – review & editing. Anne M. Alexander: Investigation, Writing – review & editing. Kaitlyn H. Watt: Investigation, Writing – review & editing. Emma W. Rosenblum: Investigation, Visualization, Writing – review & editing. Nicole Pihlstrom: Investigation, Writing – review & editing. Joshua L. Chase: Writing – review & editing. Nathaniel Mercaldo: Formal analysis, Writing – review & editing. Elizabeth Conner: Resources, Writing – review & editing. André – van der Kouwe: Investigation, Resources, Writing – review & editing. Matthew P. Frosch: Resources, Writing – review & editing. Jean C. Augustinack: Conceptualization, Formal analysis, Funding acquisition, Investigation, Project administration, Supervision, Visualization, Writing – original draft, Writing – review & editing. Ethics approval and consent to participate  \nAutopsy consent was obtained, and tissue was collected with allowance for tissue to be used in research under a protocol approved by the Institutional Review Board of Mass General Brigham.  \nDeclaration of competing interest  \nThe authors declare that they have no competing interests.  \nAuthor Manuscript Author Manuscript Author Ma","cbCaivdABlofbQzz","https://ap.wps.com/l/cbCaivdABlofbQzz","pdf",988692,24,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What problem does the study address about CA1 stereological research?\",\"answer\":\"Previous CA1 stereological studies primarily used male samples, so female total neuron counts and neuron-size data were missing or underrepresented. The study targets this gap by providing baseline data in both sexes.\"},{\"question\":\"How were CA1 total neuron counts and neuron volumes measured?\",\"answer\":\"CA1 total neuron counts and mean neuron volumes were quantified using optical fractionator and nucleator probes across human brain hemispheres.\"},{\"question\":\"What relationship did the study find between CA1 neuron counts and hippocampal volume?\",\"answer\":\"CA1 total neuron count showed a positive correlation with hippocampal volume measured from ex vivo MRI, supporting earlier findings.\"},{\"question\":\"Did age, sex, hemisphere, or p-tau pathology show evidence of association with CA1 neuron measures?\",\"answer\":\"The study reports insufficient evidence for associations between age, sex, hemisphere, or mild p-tau pathology and CA1 total neuron count, mean neuron volume, and area.\"}]","Filling in the gap - Hippocampal CA1 neuronal counts and volumes in female cognitive controls | PDF",1790671525]