Sex-Associated Cerebellar and Hippocampal Volume Reduction in Alzheimer’s Disease: Insights from the Clinical ADNI Cohort and STZ Animal Model
Abstract
1. Introduction
2. Results
2.1. Animal AD Model Phase
2.1.1. Sexually Dimorphic Cerebellar Response to STZ
2.1.2. GFAP Is Altered in Female Rats After STZ Infusion
2.1.3. Cross-Sectional Analysis Comparing Cerebellum and Hippocampus Volume with GFAP Plasma Levels in the ADNI Cohort
2.1.4. Longitudinal Analysis of Cerebellum and Hippocampus Volume Changes
3. Discussion
4. Material and Methods
4.1. STZ-ICV Animal Model Experiments
4.1.1. Chemicals
4.1.2. Animals
4.1.3. Surgical Procedure
4.1.4. The Novel Object Recognition Test (NOR)
4.1.5. ELISA for S100B and GFAP
4.1.6. Quantification of Glutathione
4.1.7. Glucose Uptake
4.1.8. Western Blot Analysis for ChAT
4.1.9. Protein Determination
4.2. Statistical Analysis
4.2.1. Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Florbetapir PET Amyloid Imaging
MRI—FreeSurfer Methods
Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Overall | ApoE4 Non-Carrier | ApoE4 Carrier | p-Value * | |
---|---|---|---|---|
N | 111 | 64 | 47 | |
N (%) | N (%) | N (%) | ||
Sex = Male | 63 (56.8) | 31 (48.4) | 32 (68.1) | 0.061 |
Race | <0.0001 | |||
Non-whites | 6 (5.4) | 5 (7.9) | 1 (2.1) | |
Whites | 105 (94.6) | 59 (92.1) | 46 (97.9) | |
Mean (SD) | Mean (SD) | Mean (SD) | ||
Diagnosis | 0.013 | |||
CN | 44 (39.6) | 30 (46.9) | 14 (29.8) | |
MCI | 49 (44.1) | 29 (45.3) | 20 (42.6) | |
Dementia | 18 (16.2) | 5 (7.8) | 13 (27.7) | |
Age | 72.07 (6.36) | 73.02 (5.94) | 70.77 (6.75) | 0.067 |
Education (years) | 16.31 (2.73) | 16.39 (2.55) | 16.19 (2.98) | 0.706 |
GFAP | 152.15 (81.26) | 151.82 (91.74) | 152.62 (65.30) | 0.959 |
Whole Cerebellum (SUVR) | 126,657.09 (12,057.85) | 124,737.36 (11,382.75) | 129,271.19 (12,574.43) | 0.05 |
Hippocampus volume (mm3) | 7494.86 (984.53) | 7568.33 (903.69) | 7394.83 (1087.06) | 0.361 |
ApoE4 Non-Carrier | ApoE4 Carrier | ||||
---|---|---|---|---|---|
Predictor | Outcome | β | p-Value | β | p-Value |
Model 1 | |||||
GFAP | Whole Cerebellum Vol. SUVR | −0.002124 | 0.0354 | 0.0005056 | 0.515 |
Total Hippocampus vol (mm3) | −0.5919 | 0.64735 | −7.598 | 0.00097 | |
Model 2 | |||||
GFAP | Whole Cerebellum Vol. SUVR | −0.002046 | 0.04599 | 0.0003038 | 0.696 |
Total Hippocampus vol (mm3) | −0.6497 | 0.61217 | −6.504 | 0.00465 |
Male | Female | ||||
---|---|---|---|---|---|
Predictor | Outcome | β | p-Value | β | p-Value |
Model 1 | |||||
GFAP | Whole Cerebellum Vol. SUVR | −0.0006723 | 0.3718 | −0.0008029 | 0.566 |
Total Hippocampus vol (mm3) | −6.937 | 0.000904 | −8.36 × 10−2 | 0.949968 | |
Model 2 | |||||
GFAP | Whole Cerebellum Vol. SUVR | −0.0006808 | 0.3701 | −0.000828 | 0.563 |
Total Hippocampus vol (mm3) | −6.721 | 0.000942 | 0.06878 | 0.958013 |
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Wartchow, K.M.; Rodrigues, L.; Dartora, W.J.; Biasibetti, R.; Selistre, N.G.; Lazarian, A.; Barrios-Castellanos, C.; Bartelo, N.; Gonçalves, C.-A.; McIntire, L.B.J.; et al. Sex-Associated Cerebellar and Hippocampal Volume Reduction in Alzheimer’s Disease: Insights from the Clinical ADNI Cohort and STZ Animal Model. Int. J. Mol. Sci. 2025, 26, 4810. https://doi.org/10.3390/ijms26104810
Wartchow KM, Rodrigues L, Dartora WJ, Biasibetti R, Selistre NG, Lazarian A, Barrios-Castellanos C, Bartelo N, Gonçalves C-A, McIntire LBJ, et al. Sex-Associated Cerebellar and Hippocampal Volume Reduction in Alzheimer’s Disease: Insights from the Clinical ADNI Cohort and STZ Animal Model. International Journal of Molecular Sciences. 2025; 26(10):4810. https://doi.org/10.3390/ijms26104810
Chicago/Turabian StyleWartchow, Krista Mineia, Leticia Rodrigues, William Jones Dartora, Regina Biasibetti, Nicholas Guerini Selistre, Artur Lazarian, Carmen Barrios-Castellanos, Nicholas Bartelo, Carlos-Alberto Gonçalves, Laura Beth J. McIntire, and et al. 2025. "Sex-Associated Cerebellar and Hippocampal Volume Reduction in Alzheimer’s Disease: Insights from the Clinical ADNI Cohort and STZ Animal Model" International Journal of Molecular Sciences 26, no. 10: 4810. https://doi.org/10.3390/ijms26104810
APA StyleWartchow, K. M., Rodrigues, L., Dartora, W. J., Biasibetti, R., Selistre, N. G., Lazarian, A., Barrios-Castellanos, C., Bartelo, N., Gonçalves, C.-A., McIntire, L. B. J., & on behalf of Alzheimer’s Disease Neuroimaging Initiative (ADNI). (2025). Sex-Associated Cerebellar and Hippocampal Volume Reduction in Alzheimer’s Disease: Insights from the Clinical ADNI Cohort and STZ Animal Model. International Journal of Molecular Sciences, 26(10), 4810. https://doi.org/10.3390/ijms26104810