Abstract
Sex differences in a novel transgenic mouse model of Alzheimer’s Disease
Physiology (Bethesda, Md.), Vol.39(S1)
05/2024
DOI: 10.1152/physiol.2024.39.S1.1114
Abstract
Abstract only Alzheimer’s disease (AD) is the most common form of dementia characterized by memory deficits, cognitive impairment, and presence of amyloid plaques and tau tangles in the brain. In the United States, six million people over the age of 65 live with AD, four million of whom are women. The apolipoprotein ( APOE) gene is the strongest genetic risk factor for late-onset AD, with the ε4 allele increasing AD risk relative to the ε3 allele. Mechanisms driving sex-based prevalence in the APOE4 genotype remain unknown. Previously, we have reported that female APOE4 mice develop hypertension and increased levels of vasoconstrictor angiotensin II (Ang II) in CSF with aging [FASEB J 2022: 36S1]. To better recapitulate human AD pathology and phenotype, we have recently generated unique mouse strains - 3XE4 and 3XE3 mice, by breeding human APOE4/APOE3-knockin with APPsw, PS1dE9, and tauP301S transgenes. Our goal is to study sex differences in the 3XE4 mice with AD. Blood pressure (BP, tail cuff), cognition (novel object recognition test), and cardiac function (echocardiography) were measured in both control 3XE3 (n=6) mice and 3XE4 (n=6) mice before and after Ang II (osmotic minipump, 1000 ng/kg/min). As expected, female mice weighed less than the male mice (Table). Basal BP and ejection fraction were higher in male 3XE4 mice compared to female 3XE4 mice (p<0.05). Total exploration time of novel object was significantly delayed in 3XE4 mice (p<0.05); the impairment was greater in the female 3XE4 mice. Notably, Ang II increased BP in male 3XE4 mice (151±5 mmHg) but not in female 3XE4 mice (125±2 mmHg). Unlike the 3XE3 mice, total exploration time of novel object was delayed (impaired) in both male and female 3XE4 mice at baseline and during Ang II. Although additional studies are needed to explore the underlying mechanisms, our results implicate potential sexual dimorphism in blood pressure regulation and cognition in Alzheimer’s Disease. [Formula: see text] Funding: NIH R01HL149677 and R21AG070188. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Details
- Title: Subtitle
- Sex differences in a novel transgenic mouse model of Alzheimer’s Disease
- Creators
- Cassandra N. Smith - University of Iowa, Internal MedicineNusaira Beenta Shahab - University of Iowa, Iowa City, IA, United StatesRobert M. Weiss - University of IowaKathy Zimmerman - University of IowaLiping Yang - University of IowaRasna Sabharwal - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Physiology (Bethesda, Md.), Vol.39(S1)
- Publisher
- AMER PHYSIOLOGICAL SOC
- DOI
- 10.1152/physiol.2024.39.S1.1114
- ISSN
- 1548-9213
- eISSN
- 1548-9221
- Grant note
- NIH: R01HL149677, R21AG070188
NIH R01HL149677 and R21AG070188.
- Language
- English
- Date published
- 05/2024
- Academic Unit
- Cardiovascular Medicine; Internal Medicine; Iowa Neuroscience Institute
- Record Identifier
- 9984643655002771
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