Topic: APOE4

Progressive impairment of cognition is a key clinical feature of Alzheimer’s disease (AD), characterized by the accumulation of amyloid beta-protein (Aβ), tau hyperphosphorylation, neuroinflammation, and neuronal degeneration.Cannabidiol (CBD) is a safe, non-psychoactive phytocannabinoid that exhibits immunomodulatory activity in neurodegenerative disease, may ameliorate AD symptoms and slow cognitive decline.In this study, we aimed to examine whether chronic treatment with CBD can prevent cognitive and social deficits in a rat model of sporadic AD, and whether these changes are associated wit

Among the three ApoE isoforms, ApoE4 is a major risk factor for sporadic AD due to its impact on amyloid beta (Abeta) clearance and plaque formation. Although extensive research has connected ApoE to various AD-related pathologies beyond Abeta, its association with ApoE isoforms remains an area that requires further investigation. This study aimed to elucidate the effects of ApoE isoforms on AD pathology using human ApoE Knock-In (KI) AD mouse models. First, we generated an APPNL-G-F;hApoE (ApoE Double KI) mouse model by crossing human ApoE3 or ApoE4 KI mice with APPNL-G-F KI mice. Additionall

Numerous studies have shown the involvement of Traumatic Brain Injury (TBI) in increasing the risk of developing dementia and Alzheimer’s Disease (AD) with age, yet the intricate details of how TBI could increase the risk of such afflictions remain obscure. The scarcity of research in this area can be attributed partially to the lack of suitable animal models that can carry humanized versions of the genes known to pose a risk for developing AD. We used two cohorts of 6 months old mice, each consisting of 10 animals (5 males), carrying humanized versions of Amyloid Precursor Protein (APP), Tau

Neuroinflammation, which refers to the inflammatory response occurring in various Central Nervous System (CNS) disorders, is a relatively recent concept. It involves two main types of cells: astrocytes, which play a significant role in the process, and brain myeloid cells (BMC), crucial players in neuroinflammation.Studies examining the entire genome (GWAS) have pinpointed over 30 genetic loci associated with Alzheimer's disease (AD), many of which relate to innate immunity and the function of microglia, notably the apolipoprotein E (APOE) gene. APOE4 is particularly significant, being the str

Dementia with Lewy Bodies (DLB) is the second most common neurocognitive pathology characterized by pathogenic deposition of α-synuclein-laden Lewy bodies within vulnerable neurons, including those of the hippocampus (HC). The strongest risk factor for sporadic Alzheimer’s disease (AD), and recently demonstrated for DLB, is the ε4 allele of apolipoprotein (APOE4) that is a major lipoprotein in the central nervous system playing a leading role in maintaining lipid homeostasis. Our group recently demonstrated that the APOE4 aggravates cognitive deficits in a mouse model of prodromal DLB – corrob

Alzheimer's disease (AD) is a prevalent form of dementia, primarily affecting those aged 65 and older, known as late-onset or sporadic AD (sAD). It is characterized by the accumulation of βeta-amyloid protein aggregates and tau protein neurofibrillary tangles. Recent research highlights the crucial link between AD and dysfunction in the blood-brain barrier (BBB), primarily composed of brain endothelial cells (BECs), pericytes, and astrocytes, which regulate homeostasis in the brain. Transporter-mediated regulation at the BBB is pivotal, with dysregulation implicated in AD pathology. Non-invasi

The human APOE4 genotype has been identified as a crucial risk factor for developing neurodegenerative diseases, such as Alzheimer, in elderly. However, no clear directions to generate a prevention plan for APOEε4 carriers exist nowadays. In this sense, current knowledge states that chronic neuroinflammation is a convergent point to neural diseases, contributing to neurodegeneration. Interestingly, APOE is an immunomodulatory agent, establishing a nexus between those premises. However, mechanisms underlying this association are yet to be clarified.We aimed to identify in aged transgenic mice t

Multiple studies have claimed that microglia and oligodendrocytes play an important role in the development of Alzheimer's disease (AD), but using genetic techniques such as gene editing these two types of cells in vivo is challenging as there are no efficient and specific vector tools to deliver genes to these cells. So we proposed some methods to achieve this goal. By combining viral libraries with evolutionary screening, we will screen vector tools that can specifically and efficiently infect this type of cells. First, these tools will make it easier for scientists to precisely manipulate c

Evidences linking air pollution and neurodevelopmental disorders are gaining a great support on the last years. Specifically, traffic-related air pollution (TRAP) has proven to negatively affect cognitive and behavioral development in children. Among different types of air pollutants, particulate matter (PM) is the one most linked with these adverse consequences. On the other hand, APOE is a polymorphic human gene that has three different alleles (e2, e3, e4), being the e3 the most prevalent allele in general population. Moreover, the e4 allele has been associated with increased risk of Alzhei