Topic: APP/PS1 mice

N-methyl-D-aspartate receptors (NMDARs) are key players in synaptic transmission and plasticity underlying learning and memory. Consequently, synaptic dysfunction of NMDARs has been implicated in the pathophysiology of Alzheimer´s disease (AD).Aims: to unravel possible alterations of GluN1, the obligatory subunit of NMDARs, in different excitatory synapses in the hippocampus.Methods: We used histoblot and SDS-digested freeze-fracture replica labelling (SDS-FRL) techniques.Results: Histoblots showed that GluN1 expression was significantly reduced in the caudate putamen, cortex and in the hippoc

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by early non-cognitive dysfunctions. Recent studies have reported synaptic alterations in limbic circuits in AD animal models, even before amyloid plaque appearance. The basolateral amygdala (BLA) is a critical region of the limbic system involved in diverse emotional processing, and studies in human and AD animal models have reported that it is altered in early AD. However, whether synaptic and excitability properties are altered in the BLA in AD has not been studied. In this study, we used 6-month-old APP/PS1

The endocannabinoid system (ECS) has gained attention as a potential target to treat Alzheimer’s disease (AD) due to its neuroprotective, antioxidant, and anti-inflammatory properties. Consequently, natural cannabinoids like delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have emerged as potential drugs against AD. Previous findings from our research group demonstrated that a combination of non-psychoactive doses of THC and CBD mitigates cognitive decline in an AD murine model, the APP/PS1 mice. Cognitive decline in AD is linked to the dysregulation of glutamate transmission within the

Voltage-gated CaV2.1 Ca2+ channels play a crucial role in regulating neurotransmitter release, thus contributing to processes such as learning and memory. Despite their recognised importance in neural function, there is limited information on their potential involvement in neurodegenerative conditions such as Alzheimer's disease (AD). Aims: to explore the impact of amyloid-β (Aβ) pathology on the nanoscale compartmentalization of CaV2.1-GABAB in the hippocampus.Methods: We used histoblot and SDS-digested freeze-fracture replica labelling (SDS-FRL) techniques in the CA1 field of the hippocampus

Alzheimer’s disease, a neurodegenerative disorder characterized by progressive cognitive decline and accumulation of amyloid-plaques and neurofibrillary-tangles[1], begins with microstructural damage 10-20 years before cognitive symptoms appear[2]; developing novel non-invasive approaches to characterize early Alzheimer-specific patterns has great potential to improve diagnosis. Neuroinflammation accompanies plaque formation and is a potential target for early detection[2]. Here, we aimed to test advanced MRI-based inflammation biomarkers to capture microstructural differences between APP/PS1

Aggregation of amyloid-beta (Aβ) is among the earliest pathological changes in Alzheimer's disease (AD, Kamenetz et al., 2003). In some individuals, however, memory and other cognitive functions remain intact, despite the presence of abundant Aβ pathology (Stern, 2012). This suggests that neurons and networks can recruit mechanisms that protect against Aβ pathology, a concept known as cognitive resilience (CR). Notably, this occurs in a sex-dependent manner, with greater CR in females (Buckley et al., 2019, Ossenkoppele et al., 2020).The underlying mechanisms of resilience to AD pathology rema

Alzheimer's disease (AD) is a major neurodegenerative disease characterized by a marked decline in the activity of the alpha-ketoglutarate dehydrogenase complex (AKGDHC), a key metabolite of the tricarboxylic acid (TCA) cycle. Earlier studies have shown that the calcium salt of AKG, CaAKG, increases the healthspan and lifespan in C57BL/6 mice by reducing inflammatory cytokines. Here, we demonstrate that CaAKG attenuates long-term potentiation (LTP) in an animal model of AD, APP/PS1 mice. CaAKG application during strong tetanisation converts early-LTP to late-LTP, stable for 4 hours in the CA1

Circadian disruption, notably sleep disturbances, serves as an early indicator of Alzheimer’s disease (AD), preceding symptoms like memory loss. The suprachiasmatic nucleus (SCN) governs biological rhythms and receives direct retinal input via melanopsin-expressing retinal ganglion cells (mRGCs) to synchronize with environmental light cycles. The anatomical and functional basis for circadian disruption in AD remains unclear. Here, we explore the relationships between non-visual photoreception, SCN connectome evolution, and sleep regulation in the APP/PS1 mouse model.We measured mRGCs' light-in

Alzheimer´s disease (AD) progression has been recently associated to the infiltration of CD8+ T cells into disease-affected brain parenchyma, where they tightly associate with microglial and neuronal structures. However, the functional role of CD8+ T cells in the AD brain is still elusive. Therefore, we investigated the impact of short-term CD8+ T cell ablation on neuroinflammation in transgenic AD mice (APP/PS1).CD8+ T cells ablation was performed via intraperitoneal injections of anti-CD8 antibody for three days in two-year-old APP/PS1 and wild-type male mice. Control groups received the res

The ventral hippocampus (vHPC) is particularly sensitive to the pathology of Alzheimer’s disease (AD). Proper activity of the vHPC is mediated by parvalbumin (PV) interneurons, which constitute 25% of all inhibitory GABAergic cells. They play a crucial role in processing prepulse inhibition of the acoustic startle reflex (PPI) and social memory, which are managed by the vHPC. In this study, we first investigated the vHPC-related deficits in PPI and social novelty preference in 10-month-old APP/PS1 mice, a transgenic model of AD. We found a significant impairment in startle reduction in APP/PS1

Aβ plays an important role in the pathogenesis of Alzheimer’s disease (AD), and passive immunotherapy targeting Aβ has emerged as a promising treatment approach. However, the administration of antibody drugs is limited due to many concerns. Therefore, using adeno-associated virus (AAV) gene therapy to deliver antibody drugs may introduce innovative treatment regimens for AD. We have previously shown that NP106, a novel anti-Aβ antibody, exhibits multiple therapeutic benefits for ameliorating brain Aβ burden and cognitive impairment in APP/PS1 mouse model of AD. In this study, we developed an N