The moderating effect of diet on the relationship between depressive symptoms and Alzheimer’s disease-related blood-based biomarkers

Neurobiology of Aging, Journal Year: 2025, Volume and Issue: 147, P. 213 - 222

Published: Jan. 15, 2025

Language: Английский

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Sex-specific influences of APOEε4 genotype on hippocampal neurogenesis and progenitor cells in middle-aged rats

Biology of Sex Differences, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 5, 2025

Abstract Background Alzheimer’s disease (AD) disproportionately and uniquely affects females, these sex differences are further exacerbated by the presence of Apolipoprotein (APOE) ε4 alleles, top genetic risk factor for late-onset AD. To expand our understanding about how AD might differentially influence males this study explores APOEε4 hippocampal neurogenesis microglia, key neuroplastic markers involved in pathogenesis, differently middle-aged rats. Methods A rat model expressing humanized (h) allele was characterized to examine adult (neural progenitor cells new-born neurons) immune (microglia) dentate gyrus hippocampus 13 month-old male female Results We observed basal at middle age, as wildtype rats had greater densities neural neurons than Male hAPOEε4 exhibited fewer cells, neurons, more microglia On other hand, Interestingly, females regardless genotype. Correlations were conducted elucidate any relationships between biomarkers. Notably, there a significant positive correlation negative but only Conclusion In contrast clear pattern effects on males, unaltered levels increased density neurons. Furthermore, significantly correlated within not females. This suggests that may be presenting compensatory response genotype age. Collectively, results exemplify importance thoroughly examining influences endophenotypes, it reveal sex-specific pathways protective mechanisms relevant

Language: Английский

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Menopause and Alzheimer’s disease susceptibility: Exploring the potential mechanisms

Brain Research, Journal Year: 2024, Volume and Issue: 1844, P. 149170 - 149170

Published: Aug. 18, 2024

Language: Английский

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Estradiol improves behavior in FAD transgenic mice that express APOE3 but not APOE4 after ovariectomy

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: April 29, 2024

Increasing evidence suggests that female individuals have a higher Alzheimer’s disease (AD) risk associated with post-menopausal loss of circulating estradiol (E 2 ). However, clinical data are conflicting on whether E lowers AD risk. One potential contributing factor is APOE . The greatest genetic for APOE4 , pronounced in post-menopause. Clinical impacts the response patients to replacement therapy. prevents, neutral, or promotes any positive effects unclear. Therefore, our goal was determine modulates impact behavior and pathology vivo To end, mice express human APOE3 (E3FAD) (E4FAD) overproduce Aβ42 were ovariectomized at either 4 months (early) 8 (late) treated vehicle months. In E3FAD mice, we found mitigated detrimental effect ovariectomy memory, no Aβ early paradigm only improved learning late paradigm. Although lowered E4FAD paradigm, there possibly due compared mice. learning/memory Collectively, these support idea that, presence pathology, supplementation

Language: Английский

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Microglia Signaling in Health and Disease – Implications in Sex-Specific Brain Development and Plasticity

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 165, P. 105834 - 105834

Published: July 29, 2024

Language: Английский

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The novel estrogen receptor beta agonist EGX358 and APOE genotype influence memory, vasomotor, and anxiety outcomes in an Alzheimer’s mouse model

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Nov. 13, 2024

Introduction Alzheimer’s disease (AD) prevalence and severity are associated with increased age, female sex, apolipoprotein E4 (APOE4) genotype. Although estrogen therapy (ET) effectively reduces symptoms of menopause including hot flashes anxiety, can reduce dementia risk, it is risks breast uterine cancer due to receptor alpha (ERα)-mediated increases in cell proliferation. Because ERβ activation this proliferation, selective targeting may provide a safer method improving memory reducing menopausal women, those AD. APOE genotype influences the response ET, although unknown whether effects vary by Methods Here, we tested ability long-term oral treatment novel highly agonist, EGX358, enhance object recognition spatial memory, drug-induced flashes, influence anxiety-like behaviors mice expressing 5 familial AD mutations (5xFAD-Tg) human APOE3 (E3FAD) or APOE4 (E3/4FAD). Mice were ovariectomized at months age then treated orally vehicle (DMSO) EGX358 (10 mg/kg/day) via hydrogel for 8 weeks. Spatial placement (OP) (OR) tasks, respectively, open field (OF) elevated plus maze (EPM). Hot flash-like (change tail skin temperature) measured following injection neurokinin agonist senktide (0.5 mg/kg). Results enhanced E3FAD E3/4FAD but did not affect memory. also reduced senktide-induced temperature elevations E3FAD, E3/4FAD, females. body weight. Discussion These data indicate that agonism facilitate both homozygotes APOE3/4 heterozygotes, only magnitude flash homozygotes, suggesting blunt beneficial ET on flashes. Collectively, these suggest potentially effect females AD-like pathology, plays an important role responsiveness.

Language: Английский

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APOE2 Heterozygosity Reduces Hippocampal Soluble Amyloid-β42 Levels in Non-Hyperlipidemic Mice

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 97(4), P. 1629 - 1639

Published: Jan. 30, 2024

APOE2 lowers Alzheimer’s disease (AD) risk; unfortunately, the mechanism remains poorly understood and use of mice models is problematic as homozygosity associated with hyperlipidemia. In this study, we developed that are heterozygous for APOE3 or APOE4 overexpress amyloid-β peptide (Aβ) (EFAD) to evaluate effect dosage on Aβ pathology. We found do not exhibit Hippocampal but cortical levels soluble Aβ42 followed order E2/2FAD > E2/3FAD≤E3/3FAD E2/4FAD < E4/4FAD without an insoluble Aβ42. These findings offer initial insights impact

Language: Английский

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The effects of APOE4 and familial Alzheimer's disease mutations on free fatty acid profiles in mouse brain are age‐ and sex‐dependent

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: July 13, 2024

APOE4 encoding apolipoprotein (Apo)E4 is the strongest genetic risk factor for Alzheimer's disease (AD). ApoE key in intercellular lipid trafficking. Fatty acids are essential brain integrity and cognitive performance implicated neurodegeneration. We determined sex- age-dependent effect of AD on free fatty acid (FFA) profiles. FFA profiles were by LC-MS/MS hippocampus, cortex, cerebellum female male, young (≤3 months) older (>5 months), transgenic APOE3 mice with without five familial (FAD) mutations (16 groups; n = 7-10 each). In different regions, females had higher levels than males either saturated or polyunsaturated FFAs both. hippocampus males, but not FAD each induced 1.3-fold almost all FFAs. females, to a less extent APOE4-induced shifts among saturated, monounsaturated, affecting total levels. cortex cerebellum, only minor effects individual The three regions strongly dependent sex age, particularly hippocampus. Here, most that affected similarly APOE4. Since hippocampal already at these alterations may modulate pathogenesis AD.

Language: Английский

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PM2.5 exposure elevates hepatic injury in hyperlipidemic mice via ROS-pyroptosis signaling pathway

Environmental Pollutants and Bioavailability, Journal Year: 2024, Volume and Issue: 36(1)

Published: Nov. 23, 2024

Language: Английский

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