Sexual dimorphism, altered hippocampal glutamatergic neurotransmission, and cognitive impairment in APP knock-in mice.

Background: It is well established that glutamatergic neurotransmission plays an essential role in learning and memory. Previous studies indicate that glutamate dynamics shift with Alzheimer's disease (AD) progression, contributing to negative cognitive outcomes.

Objective: In this study, we characterized hippocampal glutamatergic signaling with age and disease progression in a knock-in mouse model of AD (APP).

Senolytic intervention improves cognition, metabolism, and adiposity in female APP mice.

Senescent cells accumulate throughout the body and brain contributing to unhealthy aging and Alzheimer's disease (AD). The APP amyloidogenic AD mouse model exhibits increased markers of senescent cells and the senescence-associated secretory phenotype (SASP) in visceral white adipose tissue and the hippocampus before plaque accumulation and cognitive decline. We hypothesized that senolytic intervention would alleviate cellular senescence thereby improving spatial memory in APP mice.

Thermotherapy has Sexually Dimorphic Responses in APP/PS1 Mice.

A thermoregulatory decline occurs with age due to changes in muscle mass, vasoconstriction, and metabolism that lowers core body temperature (Tc). Although lower Tc is a biomarker of successful aging, we have previously shown this worsens cognitive performance in the APP/PS1 mouse model of Alzheimer's disease (AD) [1]. We hypothesized that elevating Tc with thermotherapy would improve metabolism and cognition in APP/PS1 mice.

Senolytic Intervention Improves Cognition, Metabolism, and Adiposity in Female APP Mice.

Senescent cells accumulate throughout the body and brain contributing to unhealthy aging and Alzheimer's disease (AD). The APP amyloidogenic AD mouse model exhibits increased markers of senescent cells and the senescence-associated secretory phenotype (SASP) in visceral white adipose tissue before plaque accumulation and cognitive decline. We hypothesized that senolytic intervention would alleviate cellular senescence thereby improving spatial memory in APP mice.

Sexual Dimorphism, Altered Hippocampal Glutamatergic Neurotransmission and Cognitive Impairment in APP Knock-In Mice.

Background: It is well established that glutamatergic neurotransmission plays an essential role in learning and memory. Previous studies indicate that glutamate dynamics shift with Alzheimer's disease (AD) progression, contributing to negative cognitive outcomes.

Objective: In this study, we characterized hippocampal glutamatergic signaling with age and disease progression in a knock-in mouse model of AD (APP).

Prodromal Glutamatergic Modulation with Riluzole Impacts Glucose Homeostasis and Spatial Cognition in Alzheimer's Disease Mice.

Background: Prior research supports a strong link between Alzheimer's disease (AD) and metabolic dysfunction that involves a multi-directional interaction between glucose, glutamatergic homeostasis, and amyloid pathology. Elevated soluble amyloid-β (Aβ) is an early biomarker for AD-associated cognitive decline that contributes to concurrent glutamatergic and metabolic dyshomeostasis in humans and male transgenic AD mice. Yet, it remains unclear how primary time-sensitive targeting of hippocampal glutamatergic activity may impact glucose regulation in an amyloidogenic mouse model.