Alterations in Cardiovascular Parameters in 5xFAD Murine Model

Q: What is the clinical evidence from this study?

Population: Alzheimer's disease (5xFAD murine model) (n=30). Intervention: 5xFAD transgenic Alzheimer's disease genotype vs. Wild-type littermate controls (C57BL/6J-WT). Primary outcome: Aortic impedance-based pulse wave velocity (aPWVZ, cm/s) (p=0.350).

Q: What does this research mean for the field?

At 2-3 months of age, 5xFAD mice do not exhibit significant differences in aortic or cerebral arterial stiffness despite reductions in pulse pressure, ejection time, and Tei index compared to wild-type controls. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Andrea G. Marshall; Dominique C. Stephens; Kit Neikirk; Sepiso K. Masenga; Bryanna Shao; Amber Crabtree; Zer Vue; Heather K. Beasley; Edgar Garza-López; Estêvão Scudese; Blanca Rodríguez; Han Le; Steven M. Damo; George E. Taffet; Okwute Michael Ochayi; Ronald McMillan; Jeremiah Afolabi; Vernat Exil; Ashton Oliver; Vineeta Sharma; Pamela A. Martin; Amadou Gaye; Chanel Harris; Briar Tomeau; Laura Bell; Taneisha Gillyard; R. G. Webster; Marcus Jackson; Prem Prakash; Shanilah Frierson; Chandravanu Dash; Margaret Mungai; Annet Kirabo; Jennifer A. Gaddy; Nelson Wandira; Antentor Hinton; Anilkumar K. Reddy

doi:10.1002/cbf.70138

Key result

Young 5xFAD mice show no significant change in aortic or cerebral pulse wave velocity.

P=0.350
n=30

Figures

Why the study?

Alzheimer's disease is associated with cardiovascular risk factors beyond cerebral decline, prompting evaluation of hemodynamic and arterial stiffness parameters in 5xFAD mice.

Does the 5xFAD Alzheimer's disease genotype alter cardiovascular and cerebrovascular hemodynamic and arterial stiffness parameters compared to wild-type littermates in young (2–3 month old) mice?

Key Points

To evaluate systemic cardiovascular and cerebrovascular hemodynamic parameters in young 5xFAD mice modeling Alzheimer's disease.
Evaluated 20 5xFAD mice (10 males, 10 females) and 10 littermate controls (5 males, 5 females) at 2–3 months of age under isoflurane anesthesia.
Acquired aortic outflow, mitral inflow, and carotid flow velocities using a 20 MHz Doppler probe alongside electrocardiogram signals.
Measured central aortic blood pressure with a 1-French catheter to calculate aortic impedance, cerebral impedance, and pulse wave velocities.
5xFAD mice displayed significantly lower aortic cross-sectional area, decreased aortic ejection times, and higher heart rates compared to wild-type controls.
Significant differences were observed in pulse pressure and Tei index (myocardial performance index), whereas peak aortic velocity, mean aortic velocity, and stroke distance showed no significant differences.
Impedance-based aortic and cerebral pulse wave velocity measurements did not indicate significant arterial stiffening in 5xFAD mice at 2–3 months of age.

Structured PICO

Does the 5xFAD Alzheimer's disease genotype alter cardiovascular and cerebrovascular hemodynamic and arterial stiffness parameters compared to wild-type littermates in young (2–3 month old) mice?

P

Population

30 mice at 2-3 months of age (50% female), comprising 20 5xFAD transgenic mice with Alzheimer's disease mutations and 10 C57BL/6J wild-type littermate controls evaluated at a single time point.

E

Exposure

5xFAD transgenic Alzheimer's disease mouse model (expressing human APP and PS1 mutations) evaluated under 1.5% isoflurane anesthesia via 20 MHz Doppler probe and 1-French Millar blood pressure catheter.

C

Comparator

Age- and sex-matched C57BL/6J wild-type littermate control mice fed the same standard commercial chow and evaluated under identical 1.5% isoflurane anesthesia.

O

Outcome

Cardiovascular and cerebrovascular hemodynamic and arterial stiffness parameters at 2–3 months of age, specifically impedance-based aortic pulse wave velocity (aPWVZ) and cerebral pulse wave velocity (cPWVZ).surrogate

Main Result

Absolute Event Rate: 271% vs 309%

p-value: p=0.350

Young 2–3 month old 5xFAD Alzheimer's disease mice do not yet exhibit alterations in aortic or cerebral arterial stiffness (pulse wave velocity), indicating that preclinical studies of AD-related vascular stiffness require evaluation at older ages.

Limitations

5xFAD mice lack neurofibrillary tangles which humans have in Alzheimer's disease.
Amyloid beta (Aβ) deposition levels and other molecular markers of AD pathology were not measured to correlate with pulse wave velocity.
The study only examined one time point (at 12 weeks of age), whereas cardiovascular changes may be more profound at later ages.
Peak-A mitral velocity could not be reliably measured due to fusing of the A-wave with the E-wave caused by high heart rates.
5xFAD mice lack neurofibrillary tangles that are present in human Alzheimer's disease
Did not measure amyloid-beta (Aβ) deposition levels or other molecular markers of AD pathology to correlate with pulse wave velocity
Examined only a single early time point (12 weeks / 2-3 months of age)
Could not reliably measure mitral peak-A velocity due to fusion of A-wave with E-wave at high heart rates

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

No early arterial stiffness changes in young 5xFAD mice; leaves open whether vascular alterations emerge later in Alzheimer's models.

Abstract

Alzheimer's Disease (AD) is a global health issue, affecting over 6 million people in the United States, with that number expected to increase as the population ages. As a neurodegenerative disorder that affects memory and cognitive functions, it is well established that AD is associated with cardiovascular risk factors beyond only cerebral decline. In this study, we measured hemodynamic parameters related to cardiovascular and cerebrovascular function in 5xFAD mice with AD and their littermates. Specifically, we measured cardiovascular pulse wave velocity parameters, a marker of arterial stiffness and cardiovascular risk, and cerebrovascular pulse wave velocity, a novel technique to measure cerebral arterial stiffness. Our results showed that while 5xFAD mice exhibited significant differences in ejection time, pulse pressure, and Tei index, many other cardiovascular and cerebral parameters were not different. Despite reports that amyloid plaque deposition begins at an early age of 1.5 months in 5xFAD mice, our results did not indicate significant cardiovascular changes. Studies to elucidate cardiovascular and cerebrovascular parametric changes should be done at later ages where the underlying changes are more profound.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Marshall et al. (2025) studied Alzheimer's disease (5xFAD murine model) (n=30). 5xFAD transgenic Alzheimer's disease genotype vs. Wild-type littermate controls (C57BL/6J-WT) was evaluated on Aortic impedance-based pulse wave velocity (aPWVZ, cm/s) (p=0.350). 5xFAD mice at 2-3 months of age showed no significant differences in aortic or cerebral pulse wave velocity compared to wild-type controls, despite lower pulse pressure and Tei index.

synapsesocial.com/papers/6a917fb2d61912a19af0781a https://doi.org/10.1002/cbf.70138

View Full Paper

Ask AI

Bookmark

Share

Alterations in Cardiovascular Parameters in 5xFAD Murine Model

Figures

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Alterations in Cardiovascular Parameters in 5xFAD Murine Model

Figures

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading