Sex‐biased hippocampal pathology in the 5XFAD mouse model of Alzheimer's disease: A multi‐omic analysis
Abstract
Alzheimer's disease is a progressive neurodegenerative disorder and the most common form of dementia. Like many neurological disorders, Alzheimer's disease has a sex-biased epidemiological profile, affecting approximately twice as many women as men. The cause of this sex difference has yet to be elucidated. To identify molecular correlates of this sex bias, we investigated molecular pathology in females and males using the 5XFamilial Alzheimer's disease mutations (5XFAD) genetic mouse model of Alzheimer's disease. We profiled the transcriptome and proteome of the mouse hippocampus during early stages of disease development (1, 2, and 4 months of age). Our analysis reveals 42 genes that are differentially expressed between disease and wild-type animals at 2 months of age, prior to observable plaque deposition. In 4-month-old animals, we detect 1,316 differentially expressed transcripts between transgenic and control 5XFAD mice, many of which are associated with immune function. Additionally, we find that some of these transcriptional perturbations are correlated with altered protein levels in 4-month-old transgenic animals. Importantly, our data indicate that female 5XFAD mouse exhibit more profound pathology than their male counterparts as measured by differences in gene expression. We also find that the 5XFAD transgenes are more highly expressed in female 5XFAD mice than their male counterparts, which could partially account for the sex-biased molecular pathology observed in this dataset.
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Mice from both sexes were used unless otherwise specified; when both male and female mice were used, an analysis for sex differences was performed; unless otherwise noted, no sex differences were observed.
“Given the reported sex differences in some disease pathology phenotypes46,47,62, mice from both sexes were used unless otherwise specified. When both male and female mice were used, an analysis for sex differences was performed; unless otherwise noted, no sex differences were observed.”
From Lymphoid gene expression supports neuroprotective microglia function (2025) · cites this paper as [62]
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“( For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)”
Quintanilla‐Sánchez, C., Schmitt, F. W., Curdt, N., Westhoff, A. C., Bänfer, I. W. H., Bayer, T. A., & Bouter, Y. (2023) · Biomedicines · doi:10.3390/biomedicines11020599 · Cited by 32 · see citing works
“Furthermore, a gene ontology study revealed a sex-specific molecular pattern especially in genes associated with the immune system [82].”
BackgroundOláh, V. J., Goettemoeller, A. M., Rayaprolu, S., Dammer, E. B., Seyfried, N. T., Rangaraju, S., Dimidschstein, J., & Rowan, M. J. (2022) · eLife · doi:10.7554/elife.75316 · Cited by 32 · see citing works
“In this study, we observed physiological changes in 7–8- week-old 5xFAD mice; however, few proteomic changes are predicted until ~4 months of age in this model ( Bundy et al., 2019 ).”
InfluentialGossypetin ameliorates 5xFAD spatial learning and memory through enhanced phagocytosis against Aβ
Jo, K. W., Lee, D., Cha, D. G., Oh, E.-J., Choi, Y. H., Kim, S., Park, E. S., Kim, J. K., & Kim, K. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-01096-3 · Cited by 32 · see citing works
“We used only female mice for our experiments because they were reported to show more profound AD pathology [14].”
MethodMarazuela, P., Paez-Montserrat, B., Bonaterra-Pastra, A., Solé, M., & Hernández-Guillamon, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094972 · Cited by 31 · see citing works
“The prevalence of CAA pathology increases in the presence of dementia and is particularly high in patients with Alzheimer’s disease (AD) [7,8].”
BackgroundLymphoid gene expression supports neuroprotective microglia function
Ayata, P., Crowley, J. M., Challman, M. F., Sahasrabuddhe, V., Gratuze, M., Werneburg, S., Ribeiro, D., Hays, E. C., Durán-Laforet, V., Faust, T. E., et al. (2025) · Nature · doi:10.1038/s41586-025-09662-z · Cited by 32 · see citing works
Wilson, C. A., Fouda, S. E. E., & Sakata, S. (2020) · Scientific Reports · doi:10.1038/s41598-020-72421-9 · Cited by 28 · see citing works
Cholinergic neurodegeneration in Alzheimer disease mouse models
Shekari, A., & Fahnestock, M. L. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-819973-2.00013-7 · Cited by 27 · see citing works
Boeddrich, A., Haenig, C., Neuendorf, N., Blanc, E., Ivanov, A., Kirchner, M., Schleumann, P., Bayraktaroğlu, I., Richter, M., Molenda, C., et al. (2023) · Genome Medicine · doi:10.1186/s13073-023-01206-2 · Cited by 27 · see citing works
Characterization of Apathy-Like Behaviors in the 5xFAD Mouse Model of Alzheimer's Disease
Keszycki, R. M., Rodríguez, G., Dunn, J. T., Locci, A., Orellana, H., Haupfear, I., Dominguez, S., Fisher, D. W., & Dong, H. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2023.02.012 · Cited by 27 · see citing works
Iron Responsive Element-Mediated Responses to Iron Dyshomeostasis in Alzheimer’s Disease
Hin, N., Newman, M., Pederson, S., & Lardelli, M. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210200 · Cited by 28 · see citing works
“7B) and with a previous transcriptome analysis suggesting immune activation in 5XFAD mice as early as 2–4 months[68].”
Obesity during preclinical Alzheimer's disease development exacerbates brain metabolic decline
Anderson, T., Sharma, S. K., Kelberman, M. A., Ware, C. B., Guo, N., Qin, Z. S., Weinshenker, D., & Parent, M. B. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15900 · Cited by 26 · see citing works
“Sample sizes were chosen for transcriptional analysis based on similar studies (Bundy et al., 2019; Nam et al., 2017) and for behavior testing based on our previous work (Cissé et al., 2008 ; Degroot & Parent, 2000 ; Parent et al., 1997; Shah & Parent, 2004 ).”
MethodSpeers, A. B., García‐Jaramillo, M., Feryn, A. B., Matthews, D. G., Lichtenberg, T., Caruso, M. A., Wright, K. M., Quinn, J. F., Stevens, J. F., Maier, C. S., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.788312 · Cited by 26 · see citing works
“Studies in 5xFAD mice have found that female mice display greater molecular pathology (Sadleir et al., 2015; Bundy et al., 2019), higher levels of cerebral Aβ42 (Sadleir et al., 2015), and a greater Aβ plaque burden than male mice (Bhattacharya et al., 2014; Reid and Darvesh, 2015).”
BackgroundA novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential
Greenfield, S. A., Cole, G. M., Coen, C. W., Frautschy, S. A., Singh, R. P., Mekkittikul, M., Garcia‐Ratés, S., Morrill, P. R., Hollings, O., Passmore, M., et al. (2022) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12274 · Cited by 26 · see citing works
Garcia‐Segura, M. E., Durainayagam, B. R., Liggi, S., Graça, G., Jiménez, B., Dehghan, A., Tzoulaki, I., Karaman, İ., Elliott, P., & Griffin, J. L. (2022) · Journal of Neurochemistry · doi:10.1111/jnc.15719 · Cited by 25 · see citing works
“…et al., 2019) and has been previously applied to AD data to infer metabolic perturbations using protein ranking and gene- set enrichment (Bai et al., 2020; Bundy et al., 2019), gene– protein interaction networks (Canchi et al., 2019), and protein– protein interaction networks (Zhang et al., 2020).”
MethodComplexity of Sex Differences and Their Impact on Alzheimer’s Disease
Kadlecová, M., Freude, K., & Haukedal, H. (2023) · Biomedicines · doi:10.3390/biomedicines11051261 · Cited by 26 · see citing works
“However, these female mice also showed elevated expression of the 5xFAD transgenes, which could have accounted for the sex-related differential upregulation in transcriptome [201].”
BackgroundBouter, C., Irwin, C., Franke, T. N., Beindorff, N., & Bouter, Y. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.745064 · Cited by 24 · see citing works
Familial natural short sleep mutations reduce Alzheimer pathology in mice
Dong, Q., Gentry, N. W., McMahon, T., Yamazaki, M., Benitez-Rivera, L., Wang, T., Gan, L., Ptáček, L. J., & Fu, Y. (2022) · iScience · doi:10.1016/j.isci.2022.103964 · Cited by 21 · see citing works
“This is not surprising because female 5XFAD mice have been shown to have more robust pathology than males (Bundy and Vied, 2019).”
BackgroundSex differences and the role of estrogens in the immunological underpinnings of Alzheimer's disease
Price, B. R., Walker, K. A., Eissman, J. M., Suryadevara, V., Sime, L. N., Hohman, T. J., & Gordon, M. N. (2025) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.70139 · Cited by 23 · see citing works
A multifaceted role of progranulin in regulating amyloid-beta dynamics and responses
Du, H., Wong, M. Y., Zhang, T., Santos, M. N., Hsu, C., Zhang, J., Yu, H., Luo, W., & Hu, F. (2021) · Life Science Alliance · doi:10.26508/lsa.202000874 · Cited by 19 · see citing works
Saha, P., Weigle, I. Q., Slimmon, N., Poli, P. B., Patel, P. A., Zhang, X., Cao, Y., Michalkiewicz, J., Gomm, A., Zhang, C. M., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-52246-6 · Cited by 20 · see citing works
“Studies using transgenic mouse models of AD have shown that hormonal fluctuations during the estrus cycle can impact Aβ accumulation, tau pathology, neuroinflammation, and synaptic function 25,33,34 .”
BackgroundMinding the Gap: Exploring Neuroinflammatory and Microglial Sex Differences in Alzheimer’s Disease
Reed-Geaghan, E. G., & Keller-Norrell, P. R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417377 · Cited by 19 · see citing works
Lauer, A. A., Janitschke, D., Guilherme, M. D. S., Nguyen, V. T. T., Bachmann, C. M., Qiao, S., Schrul, B., Boehm, U., Grimm, H. S., Hartmann, T., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-94706-3 · Cited by 18 · see citing works
Kim, D.-H., Jang, Y.-S., Jeon, W. K., & Han, J. (2019) · Experimental Neurobiology · doi:10.5607/en.2019.28.2.146 · Cited by 18 · see citing works
5XFAD mice show early-onset gap encoding deficits in the auditory cortex
Weible, A. P., Stebritz, A. J., & Wehr, M. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.05.013 · Cited by 17 · see citing works
“In the present study, behavioral gap detection in female 5XFAD mice was more impaired at 2–4 months relative to both controls and male 5XFAD mice, the same age as when other sexlinked differences in 5XFAD mice have been observed (Bundy et al., 2019; Prange-Kiel et al., 2016).”
BackgroundCuddy, L. K., Alia, A. O., Salvo, M. A., Chandra, S., Grammatopoulos, T. N., Justman, C. J., Lansbury, P. T., Mazzulli, J. R., & Vassar, R. J. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00561-9 · Cited by 17 · see citing works
Daini, E., Secco, V., Liao, W., Zoli, M., & Vilella, A. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.135869 · Cited by 15 · see citing works
Sinnige, T., Stroobants, K., Dobson, C. M., & Vendruscolo, M. (2020) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583520000025 · Cited by 18 · see citing works
“A combined proteomics and genomics study on the 5xFAD mouse has also revealed changes in the expression of genes related to immune function, prior to the onset of Aβ plaque deposition (Bundy et al., 2019).”
BackgroundSinnige, T., Stroobants, K., Dobson, C. M., & Vendruscolo, M. (2020) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583520000104 · Cited by 15 · see citing works
Guo, C., Wang, T., Zhang, D., Ge, X., & Li, J. (2023) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2023.02.078 · Cited by 13 · see citing works
Xu, C., Mei, Y., Yang, R., Luo, Q., Zhang, J., Kou, X., Hu, J., Wang, Y., Li, Y., Chen, R., et al. (2024) · Cell & Bioscience · doi:10.1186/s13578-024-01230-8 · Cited by 11 · see citing works
“Previous findings have shown that female 5 × FAD transgenic mice have more serious pathology [32] and heightened inflammation versus males [33].”
BackgroundCopper Modulation and Memory Impairment due to Hippocampal Tau Pathology
Harris, C., Gray, N. E., Caruso, M. A., Hunter, M., Ralle, M., & Quinn, J. F. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200002 · Cited by 11 · see citing works
Zhai, Y., Haresi, A. J., Huang, L., & Lang, D. (2019) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12821 · Cited by 11 · see citing works
Alzheimer’s Disease Progression in the 5×FAD Mouse Captured with a Multiplex Gene Expression Array
Gatt, A. P., Whitfield, D., Ballard, C. G., Doherty, P., & Williams, G. H. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190805 · Cited by 8 · see citing works
“Female mice are thought to have slightly altered transcriptomic changes in relation to estrogen levels [57] and therefore gender-related changes must be taken into account in future studies.”
Pan, A. L., Audrain, M., Sakakibara, E., Joshi, R., Zhu, X., Wang, Q., Wang, M., Beckmann, N. D., Schadt, E. E., Gandy, S., et al. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1400447 · Cited by 9 · see citing works
“…variability in gene expression resulting from the mixed B6/SJL genetic background compared to previous studies where higher numbers of DEGs were detected in 4 month old male 5xFAD on a C57BL/6J background (537 DEGs) (Bundy et al., 2019), we used less stringent parameters to filter DEGs ( p 0.05).”
MethodInfluentialLiu, X., Hike, D., Choi, S., Man, W., Ran, C., Zhou, X. A., Jiang, Y., & Yu, X. (2024) · Nature Communications · doi:10.1038/s41467-024-53878-y · Cited by 9 · see citing works
“For the AD mice, only females were used since female 5xFAD mice display more pronounced molecular changes, including cortical and hippocampal A β accumulation and other in fl ammatory gene induction, than male 5xFAD mice 64 – 66 ,118 , 119 .”
Iron Responsive Element (IRE)-mediated responses to iron dyshomeostasis in Alzheimer’s diseasePreprint
Hin, N., Newman, M., Pederson, S., & Lardelli, M. T. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.01.071498 · Cited by 9 · see citing works
“This is consistent with an enrichment of immune-related Hallmark gene sets that we observed in this age group (see Figure 7B) and with a previous transcriptome analysis suggesting immune activation in 5XFAD mice as early as 2-4 months [42].”
ResultCorrelations of blood and brain NMR metabolomics with Alzheimer’s disease mouse models
Knörnschild, F., Zhang, E. J., Biswas, R. G., Kobus, M., Chen, J., Zhou, J., Rao, A., Sun, J., Wang, X., Li, W., et al. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03293-8 · Cited by 8 · see citing works
Anschuetz, A., Schwab, K., Harrington, C. R., Wischik, C. M., & Riedel, G. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251362212 · Cited by 7 · see citing works
Air pollution exposure increases ABCB1 and ASCT1 transporter levels in mouse cortex
Puris, E., Saveleva, L., Górová, V., Vartiainen, P., Kortelainen, M., Lamberg, H., Sippula, O., Malm, T., Jalava, P., Auriola, S. O. K., et al. (2022) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2022.104003 · Cited by 8 · see citing works
Möller, J. E. L., Schmitt, F. W., Günther, D., Stöver, A., & Bouter, Y. (2024) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2024.173944 · Cited by 7 · see citing works
“In comparison to males, female 5XFAD mice exhibited elevated levels of human APP and amyloid, along with increased inflammation (Bundy et al., 2019; Devi et al., 2010; Forner et al., 2021; Poon et al., 2023; Sil et al., 2022).”
Progressive Hippocampal Neuroarchitecture Changes in the 5×FAD Alzheimer’s Disease Mouse Model
Jang, H., Lee, S., Kim, Y.-J., Lee, J., Kim, S.-W., Son, Y., Kim, J., Park, J., Youn, B., & Moon, C. (2025) · Journal of Integrative Neuroscience · doi:10.31083/jin40831 · Cited by 5 · see citing works
“First, all experiments were conducted using only female 5 × FAD mice to reduce variability related to sex-dependent transgene expression and behavioral phenotypes [89,90], which may limit the generalizability across sexes.”
Behrens, L. M. P., Fernandes, G. D. S., Gonçalves, G. F., Nunes, F. V. M., Weimer, R. D., Moreira, J. C. F., & Dorn, M. (2026) · Neuroscience · doi:10.1016/j.neuroscience.2026.01.019 · Cited by 6 · see citing works
Zhu, C., Ren, X., Liu, C., Liu, Y., & Wang, Y. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.382254 · Cited by 6 · see citing works
Campbell, K. J., Jiang, P., Olker, C. J., Lin, X., Kim, S. Y., Lee, C., Song, E. J., Turek, F. W., & Vitaterna, M. H. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1430989 · Cited by 6 · see citing works
Araya, J., Garay, S., Rojas, C., Duran-Aniotz, C. A., Palacios, A. G., Chacón, M., & Medina, L. E. (2022) · Scientific Reports · doi:10.1038/s41598-022-12208-2 · Cited by 6 · see citing works
Ohno, M. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-231451 · Cited by 5 · see citing works
“Importantly, 5XFAD mice manifesting ALF at 4 months of age [24, 39] already show early AD-like proteomic signature including an increase in GFAP expression [115, 116] and GFAP-immunoreactive astrocytes in the brain [40].”
Marongiu, R., Platholi, J., Park, L., Yu, F., Sommer, G., Woods, C., Milner, T. A., & Glass, M. J. (2025) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2025.1597130 · Cited by 5 · see citing works
Alterations in odor hedonics in the 5XFAD Alzheimer’s disease mouse model and the influence of sex.
Roberts, E. R., Dossat, A. M., Cortijo, M. D. M., Brundin, P., & Wesson, D. W. (2020) · Behavioral Neuroscience · doi:10.1037/bne0000400 · Cited by 4 · see citing works
Kapphan, L. M., Nguyen, V. T. T., Heinrich, I., Tüscher, O., Passauer, P., Schwiertz, A., & Endres, K. (2023) · Microorganisms · doi:10.3390/microorganisms11122856 · Cited by 4 · see citing works
“Surprisingly, female 5xFAD mice have been shown to have more severe pathology, as evidenced by gene expression in 4-month-old animals [44] and A β deposition as well as hematogenous macrophage accumulation surrounding plaques [45].”
BackgroundAberrant Cortical Activity in 5xFAD Mice in Response to Social and Non-Social Olfactory Stimuli
Kosel, F., Hartley, M. R., & Franklin, T. B. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230858 · Cited by 4 · see citing works
“…genes associated with neuropathology by 4 months of age, including the mutated APP and PSEN1 transgenes responsible for driving the AD-related pathology exhibited by this model [101], consistent with increased A (cid:2) pathology observed in females compared to males at 3 and 6 months of age [102].”
Sex still matters for the brain and mental health across the lifespan
Beltz, A. M., Tronson, N. C., Singh, M., & Rezq, S. (2025) · Biology of Sex Differences · doi:10.1186/s13293-025-00710-x · Cited by 4 · see citing works
“Similarly, females show more neuropathological features of AD, such as amyloid plaques, tau deposition, and neurofibrillary tangles (NFT) [18, 19].”
Neuharth, J., Hernandez, K., Bernholtz, J., Edwards, H., & Stewart, A. (2025) · Biology of Sex Differences · doi:10.1186/s13293-025-00788-3 · Cited by 4 · see citing works
Proteomic Signaling of Dual-Specificity Phosphatase 4 (DUSP4) in Alzheimer’s Disease
Wang, E., Pan, A. L., Bagchi, P., Rangaraju, S., Seyfried, N. T., Ehrlich, M. E., Salton, S. R., & Zhang, B. (2024) · Biomolecules · doi:10.3390/biom14010066 · Cited by 3 · see citing works
Damborsky, J. C., & Yakel, J. L. (2024) · Journal of Molecular Neuroscience · doi:10.1007/s12031-024-02260-0 · Cited by 2 · see citing works
“…of a more severe phenotype, including more severe molecular pathology, increased anxiety, increased expression of inflammatory markers, more pronounced changes in gene expression, and stress-induced increases in Aβ (Devi et al. 2010; Bundy et al. 2019; Oblak et al. 2021; Sil et al. 2022).”
BackgroundRodrigues, K. D. C., Oliveira, M. D. C., de Souza, I. C., Igansi, A. W., Lopes, A. V. B., Pacheco, C. O., Haas, S. E., Schumacher, R. F., & Luchese, C. (2025) · Psychopharmacology · doi:10.1007/s00213-025-06967-9 · Cited by 2 · see citing works
Nitzan, K., Bentulila, Z., Bregman-Yemini, N., Ayalon, N., David, D., Break, E. P., Sarne, Y., & Doron, R. (2026) · Biology of Sex Differences · doi:10.1186/s13293-025-00815-3 · Cited by 2 · see citing works
“These sex-specific differences point to distinct neural strategies for memory and learning, influenced by both sex-dependent brain pathology and task demands [38].”
Karthivashan, G., Wang, S., Wu, Q., Dahal, A., Li, X., Galleguillos, D., Sipione, S., Thinakaran, G., & Kar, S. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71348 · Cited by 2 · see citing works
Boeddrich, A., Haenig, C., Neuendorf, N., Blanc, E., Ivanov, A., Kirchner, M., Schleumann, P., Bayraktaroğlu, I., Richter, M., Molenda, C., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.16.523715 · Cited by 2 · see citing works
Erofeev, A., Vinokurov, E. K., Bolshakova, A. V., Борисович, Б. И., & Власова, О. Л. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1550673 · Cited by 1 · see citing works
Marongiu, R., Platholi, J., Park, L., Yu, F., Sommer, G., Woods, C., Milner, T. A., & Glass, M. J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.14.643317 · Cited by 1 · see citing works
“Additionally, female 5xFAD mice show increased hippocampal A β and elevated expression of immune-related genes and proteins compared to age-matched males [18, 25-29].”
Boeddrich, A., Haenig, C., Neuendorf, N., Blanc, E., Ivanov, A., Kirchner, M., Schleumann, P., Bayraktaroğlu, I., Richter, M., Molenda, C., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23714235
Ringland, C., Schweig, J. E., Eisenbaum, M., Paris, D., Ait‐Ghezala, G., Mullan, M., Crawford, F., Abdullah, L. I., & Bachmeier, C. (2021) · Figshare · doi:10.6084/m9.figshare.14677003
Additional file 1 of Integrated analysis of the aging brain transcriptome and proteome in tauopathy
Mangleburg, C. G., Wu, T., Yalamanchili, H. K., Guo, C., Hsieh, Y.-C., Duong, D. M., Dammer, E. B., Jager, P. L. D., Seyfried, N. T., Liu, Z., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13024037
Boeddrich, A., Haenig, C., Neuendorf, N., Blanc, E., Ivanov, A., Kirchner, M., Schleumann, P., Bayraktaroğlu, I., Richter, M., Molenda, C., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23714229
Boeddrich, A., Haenig, C., Neuendorf, N., Blanc, E., Ivanov, A., Kirchner, M., Schleumann, P., Bayraktaroğlu, I., Richter, M., Molenda, C., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23714232
Xu, C., Mei, Y., Yang, R., Luo, Q., Zhang, J., Kou, X., Hu, J., Wang, Y., Li, Y., Chen, R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25708927
Investigating gender differences in Alzheimer's disease
Fouad, G. I., Ando, H., & Ichihara, G. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877251410204
“Moreover, there are contradicting studies regarding the impact of the estrogen response element within the promoter on the accelerated A β deposition; regarding the implication of estrogen sensitive 144,145 or non-estrogen sensitive mechanisms.”
Glycolysis-enhancing α1-adrenergic antagonists have therapeutic potential in Alzheimer’s disease
Zhang, Q., Schultz, J. L., Simmering, J. E., Kirkpatrick, B. Q., Weber, M. A., Skuodas, S., Hicks, T., Pierce, G., Laughlin, M., George, B., et al. (2026) · Alzheimer s Research & Therapy · doi:10.1186/s13195-026-02135-z
“…model [33, 49, 50], (ii) CA1 pyramidal neurons are critically involved in the spatial memory tasks we used to assess behavior, providing a structural-func-tional link [51, 52], and (iii) prior 5xFAD characterizations have established robust amyloid burden in this region by 6 months of age [53, 54].”
Giffin, K. A., Puranik, N., Bustamante, A. C., Padilla, M., Zeng, Z., Randolph, G., Wheaton, L., Moore, S. J., Newstead, M. W., Denstaedt, S. J., et al. (2026) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2026.101309
“These mice have been shown to have significant brain transcriptomic changes by 4 months of age (Bundy et al., 2019; “ Neuropathology of 034848 and 034840, ” n.d.).”
Diphenhydramine disrupts sleep architecture in 5XFAD Alzheimer's disease model and wild-type mice
Copeland, M. H., Youngstrom, D. E., Konrad, K., Diering, G. H., Letsinger, A. C., Wilson, L., Yakel, J. L., & Cushman, J. D. (2026) · Neurobiology of Sleep and Circadian Rhythms · doi:10.1016/j.nbscr.2026.100154
“Female 5XFAD mice mirror this pathology as they show more profound pathology than males; they exhibit higher levels of amyloid-beta plaque deposition, enhanced astrogliosis, and higher expression of 5XFAD transgenes (Devi et al., 2010; Poon et al., 2023; Sadleir et al., 2015; Bundy et al., 2019).”
- Authors
- Bundy, J. L., Vied, C., Badger, C., & Nowakowski, R. S.
- Affiliations
- Florida State University (US)
- Corresponding author
- Bundy, Joseph L.
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2018-11-08
- Volume
- 527
- Issue
- 2
- Pages
- 462-475
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- OpenAlex
- W2894858108
- Cited by
- 90
- References
- 67
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 11 · 2023: 16 · 2022: 15 · 2021: 16 · 2020: 9 · 2019: 5
- FWCI
- 5.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, sex differences, 5xFAD mice, hippocampus, transcriptome, proteome, differentially expressed genes, immune function, early-stage disease, transgene expression
- MeSH terms
- Aging, Alzheimer Disease, Animals, Disease Models, Animal, Female, Hippocampus, Male, Mice, Inbred C57BL, Mice, Transgenic, RNA, Messenger, Sex Characteristics, Proteome, Plaque, Amyloid, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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