Filling in the gap: Hippocampal CA1 neuronal counts and volumes in female cognitive controls

CA1 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 4461.9 ± 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. There 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 may suggest that cognitively intact males and females have similar total neuron counts and mean neuron volumes. This implies that CA1 total neuron count is not significantly contributing to the increased vulnerability of females to Alzheimer's disease.