Journal: PLoS ONE

Article Title: Evidence in support of chromosomal sex influencing plasma based metabolome vs APOE genotype influencing brain metabolome profile in humanized APOE male and female mice

doi: 10.1371/journal.pone.0225392

Figure Lengend Snippet: Fasting plasma levels of metabolic indicators of APOE3 and APOE4, male and female mice were measured at 6 months (A-D) and 16 months (E-H) old. At 6 months of age, (A) male mice had significantly higher fasting glucose levels compared to their female counterparts with the same APOE genotype. In both sexes, APOE3 mice have significant higher fasting glucose levels comparing to their APOE4 counterparts. The insulin level (B) was highest in APOE3 males whereas the triglyceride level (C) was highest in APOE4 females, though not significant. (D) Female mice exhibited significantly higher fasting ketone body level compared to their male counterparts with the same APOE genotype. APOE4 females also had significantly higher ketone body level compared to APOE3 females. At 16 months of age, no significant differences were observed in glucose levels across these four groups (E). However, APOE3 males exhibited significantly higher insulin levels (F) compared to APOE4 males and females. APOE4 females exhibited significantly higher triglyceride (G) and ketone body (H) levels compared to the other three groups. All data are presented as mean ± SEM, * P< 0.05, ** P< 0.01, *** P< 0.001.

Article Snippet: Female and male humanized APOE3 targeted replacement (hAPOE3) and APOE4 targeted replacement (hAPOE4) homozygous mice on a C57BL/6 background strain were obtained from Taconic Inc.

Techniques: Clinical Proteomics

Journal: PLoS ONE

Article Title: Evidence in support of chromosomal sex influencing plasma based metabolome vs APOE genotype influencing brain metabolome profile in humanized APOE male and female mice

doi: 10.1371/journal.pone.0225392

Figure Lengend Snippet: (A) Total plasma levels of major metabolite group of 16 months old APOE3 and APOE4, male and female mice. Amino acid (B) levels were higher in APOE4 males. Acylcarnitine (C) and sphingomyelin (D) levels were higher in APOE4 females. Phosphatidylcholine (E) levels were higher in males, while lysophosphatidylcholine(F) levels were higher in both APOE4 male and female mice.

Article Snippet: Female and male humanized APOE3 targeted replacement (hAPOE3) and APOE4 targeted replacement (hAPOE4) homozygous mice on a C57BL/6 background strain were obtained from Taconic Inc.

Techniques: Clinical Proteomics

Journal: PLoS ONE

Article Title: Evidence in support of chromosomal sex influencing plasma based metabolome vs APOE genotype influencing brain metabolome profile in humanized APOE male and female mice

doi: 10.1371/journal.pone.0225392

Figure Lengend Snippet: (A) Total cortical levels of major metabolite groups of 16 months old APOE3 and APOE4, male and female mice. Cortical levels of amino acid (B), carnitine (C) and lysophosphatidylcholine (F) were higher in APOE4 males and females. APOE3 males exhibited higher sphingomyelin (D) and phosphatidylcholines (E) levels than the other three groups.

Article Snippet: Female and male humanized APOE3 targeted replacement (hAPOE3) and APOE4 targeted replacement (hAPOE4) homozygous mice on a C57BL/6 background strain were obtained from Taconic Inc.

Techniques:

Journal: PLoS ONE

Article Title: Evidence in support of chromosomal sex influencing plasma based metabolome vs APOE genotype influencing brain metabolome profile in humanized APOE male and female mice

doi: 10.1371/journal.pone.0225392

Figure Lengend Snippet: (A) The clustering pattern of plasma metabolites from 16 months old APOE3 and APOE4, males and females were primarily separated by sex and then by APOE genotype in females only. (B) In contrast, the clustering pattern of brain metabolites were well separated by sex and APOE genotype in APOE3 carriers only whereas APOE4 males and females showed no separation.

Article Snippet: Female and male humanized APOE3 targeted replacement (hAPOE3) and APOE4 targeted replacement (hAPOE4) homozygous mice on a C57BL/6 background strain were obtained from Taconic Inc.

Techniques: Clinical Proteomics

Journal: PLoS ONE

Article Title: Evidence in support of chromosomal sex influencing plasma based metabolome vs APOE genotype influencing brain metabolome profile in humanized APOE male and female mice

doi: 10.1371/journal.pone.0225392

Figure Lengend Snippet: (A) PCA analysis of RNA-Seq transcriptome on top 500 variance genes across all Groups. (B) Differentially Expressed Genes and GSEA enriched pathways between different sex and APOE genotypes. (C-E) Average heatmap of each sex and APOE genotype groups of genes directly involved in glycolysis, β-oxidation, and TCA cycle. (F) Average heatmap of mitochondrial encoded genes in each group showed lower mt-genes in APOE4 carriers comparing to their APOE3 compartments. Overall, males exhibited a transcriptome characterized by greater glycolytic and corresponding TCA transcriptome which was augmented in APOE4 males. In contrast, females exhibited a transcriptome characterized by expression of genes required for beta oxidation of lipids with a concomitant rise in subunits required for electron transport chain complex II.

Article Snippet: Female and male humanized APOE3 targeted replacement (hAPOE3) and APOE4 targeted replacement (hAPOE4) homozygous mice on a C57BL/6 background strain were obtained from Taconic Inc.

Techniques: RNA Sequencing, Expressing

Journal: PLoS ONE

Article Title: Evidence in support of chromosomal sex influencing plasma based metabolome vs APOE genotype influencing brain metabolome profile in humanized APOE male and female mice

doi: 10.1371/journal.pone.0225392

Figure Lengend Snippet: Perfused fixed skulls of 16 months old APOE3 and APOE4 male and female mice underwent T2-weighted and diffusion-weighted imaging. T2-weighted imaging was used to conduct (A) Total brain volume measurements. (B-F) Parcellated brain regions normalized to total brain volume were plotted. (B) frontal lobe, (C) occipital lobe, (D) parieto-temporal lobe, (E) dentate gyrus of the hippocampus, (F) hippocampus proper. (G-H) Averaged value of the top-quartile of diffusion-metric fractional anisotropy for major white matter tracts(n = 2-3/group). (H) Friedman’s non-parametric rank test for fractional anisotropy of white matter tracts (G) in comparison to APOE3 males. Data presented indicate mean ± SEM, *p<0.05, **p<0.01.

Article Snippet: Female and male humanized APOE3 targeted replacement (hAPOE3) and APOE4 targeted replacement (hAPOE4) homozygous mice on a C57BL/6 background strain were obtained from Taconic Inc.

Techniques: Diffusion-based Assay, Imaging, Comparison

Journal: PLoS ONE

Article Title: Evidence in support of chromosomal sex influencing plasma based metabolome vs APOE genotype influencing brain metabolome profile in humanized APOE male and female mice

doi: 10.1371/journal.pone.0225392

Figure Lengend Snippet: Cortical Aβ42 (A) level was significantly higher in APOE4 mice compared to APOE3 mice. APOE4 females also had significantly higher Aβ40 (B) level compared to the other 3 groups. The Aβ42/40 ratio (C) was significantly higher in APOE4 males compared to females, and the ratio in both sex of APOE4 mice were significantly higher than that in APOE3 mice. All data are presented as mean ± SEM, * P< 0.05, ** P< 0.01, *** P< 0.001.

Article Snippet: Female and male humanized APOE3 targeted replacement (hAPOE3) and APOE4 targeted replacement (hAPOE4) homozygous mice on a C57BL/6 background strain were obtained from Taconic Inc.

Techniques:

Journal: Frontiers in Cell and Developmental Biology

Article Title: APOE4 Promotes Tonic-Clonic Seizures, an Effect Modified by Familial Alzheimer’s Disease Mutations

doi: 10.3389/fcell.2021.656521

Figure Lengend Snippet: APOE4 but not APOE3 is associated with tonic-clonic seizures during cage change day. The incidence of tonic-clonic seizures was evaluated during cage change day over a 5-week period in mice that express APOE3 or APOE4 in the absence (E3FAD– and E4FAD–) and presence (E3FAD+ and E4FAD+) of five familial AD mutations. (A) Tonic-clonic seizures manifested in mice that express APOE4 , but not APOE3 (* p < 0.00001, E4FAD– and E4FAD+ vs. E3FAD– and E3FAD+ mice, Fisher Exact test). (B) There were similar seizure frequencies in male and female APOE4 mice ( p = 0.70, male E4FAD– and E4FAD+ vs. female E4FAD– and E4FAD+, Chi-square test). (C) Interestingly, there were higher seizures in the absence of FAD mutations in APOE4 mice (* p < 0.0001, E4FAD– vs. E4FAD+ mice, Chi-square test). n = 23 male E3FAD–, 25 female E3FAD–, 58 male E4FAD–, 34 female E4FAD–, 28 male E3FAD+, 29 female E3FAD+, 46 male E4FAD+, 37 female E4FAD+ mice.

Article Snippet: As with APOE4 , a similar frequency of total seizures was observed between male (86.7%, 13/15 male) and female APOE3 mice (63.2%, 12/19 female) ( p = 0.12, male E3FAD- and E3FAD+ vs. female E3FAD− and E3FAD+, Chi-square test) with similar seizure distribution (9/13 male, 11/12 female, ).

Techniques:

Journal: Frontiers in Cell and Developmental Biology

Article Title: APOE4 Promotes Tonic-Clonic Seizures, an Effect Modified by Familial Alzheimer’s Disease Mutations

doi: 10.3389/fcell.2021.656521

Figure Lengend Snippet: Higher seizures with APOE4 for pentylenetetrazole-induced seizures. Seizure frequency was evaluated in EFAD mice after treatment with pentylenetetrazole (PTZ, 60 mg/kg), which resulted in a range of seizure-like behaviors from freezing and myoclonic twitches to tonic-clonic seizures. (A) Seizure behaviors were modulated by APOE genotype and were higher with APOE4 in EFAD mice (* p < 0.028, E4FAD– and E4FAD+ vs. E3FAD– and E3FAD+ mice, Chi-square test). (B) With APOE4 expression, in male (12/16) and female (17/19) mice there was a similar distribution of seizures (tonic-clonic compared to total, p = 0.26, male E4FAD– and E4FAD + vs. female E4FAD– and E4FAD+, Chi-square test). (C) However, there was higher distribution of tonic-clonic seizures in E4FAD+ (19/20) compared to E4FAD– (10/15) mice (* p = 0.028, E4FAD– vs. E4FAD+ mice, Chi-square test). With APOE3 expression (D) tonic-clonic seizure frequency was also similar for each sex ( p = 0.16, 9/13 male E3FAD– and E3FAD+ vs. 11/12 female E3FAD– and E3FAD+, Chi-square test). (E) Although not statistically significant, there was trend of higher tonic-clonic seizure incidence with FAD mutations ( p = 0.07, 7/11 E3FAD– vs. 13/14 E3FAD+ mice, Chi-square test). n = 6 male E3FAD–, 11 female E3FAD–, 8 male E4FAD–, 8 female E4FAD–, 9 male E3FAD+, 8 female E3FAD+, 9 male E4FAD+, 11 female E4FAD+.

Article Snippet: As with APOE4 , a similar frequency of total seizures was observed between male (86.7%, 13/15 male) and female APOE3 mice (63.2%, 12/19 female) ( p = 0.12, male E3FAD- and E3FAD+ vs. female E3FAD− and E3FAD+, Chi-square test) with similar seizure distribution (9/13 male, 11/12 female, ).

Techniques: Expressing