Switch Therapeutics Inc. has announced its first development candidate, a liver-sparing APOE (apolipoprotein E) RNAi therapy for treatment of Alzheimer’s disease in APOE4 carriers. Switch’s conditionally activated siRNA (CASi)-APOE program is designed to knock down APOE in the CNS without affecting APOE in the liver, where it plays a vital role in systemic lipid homeostasis.
Based on its analysis of a large cohort of individuals homozygous for the ε4 variant of apolipoprotein E (APOE4), a multinational team of researchers is arguing that homozygosity for APOE4 should be considered a genetic form of Alzheimer’s disease. However, not everyone agrees that the findings warrant reclassifying APOE from risk factor to causal gene. Currently, APOE4 is classified as the strongest risk factor for developing AD. Another variant, the APOE2 variant, is protective, while APOE3 is neutral.
Based on its analysis of a large cohort of individuals homozygous for the ε4 variant of apolipoprotein E (ApoE4), a multinational team of researchers is arguing that homozygosity for ApoE4 should be considered a genetic form of Alzheimer’s disease (AD).
By using machine learning techniques to scour electronic health records, researchers have identified individuals who were likely to have binge eating disorder (BED) but had not received a formal diagnosis. Genomewide association studies including such patients enabled the investigators to identify several risk variants that were correlated with BED irrespective of body mass index (BMI), which covaries with BED and is a potential confounding factor.
Investigators have identified a second individual who remained cognitively normal into his late 60s despite having the PSEN1 E280A mutation, which causes a familial version of early-onset Alzheimer’s disease (AD). The likely source of protection, a mutation in a gene called Reelin, is distinct from the protective mechanism identified in the first case of an individual who was protected from the effects of PSEN1 E280A. That case was reported in 2019.
Androgen deprivation therapy (ADT) is still the main treatment option for locally advanced and metastatic prostate cancer (PCa); however, most patients receiving ADT develop resistance to treatment and relapse, with a more aggressive form of cancer, castration-resistant prostate cancer (CRPC).
The factors why the clinical outcomes during infection with SARS-CoV-2 virus are highly heterogenous remains poorly understood. Apolipoprotein E (APOE) is a secreted protein with roles in lipid metabolism; interestingly, APOE has been shown to modulate immunity, including infection and antitumor immunity.
Despite the identification of the APOE gene as the strongest genetic link to late-onset Alzheimer's disease (AD) since 1993 and the subsequent advances in the understanding of AD pathogenesis, the development of effective consensus-directed treatment therapies has yet to be realized.
Researchers report in the June 21, 2021, online issue of Neuron that overexpression of the LDL receptor can reduce ApoE to prevent tauopathy-associated neurodegeneration in mouse models.
A study led by scientists at the University of Science and Technology of China in Hefei City is the first to show that astrocytic apolipoprotein E (ApoE) regulates neuronal epigenetic states via reprogramming lipid metabolism, which was shown to control brain function, in particular memory consolidation, in mice.
