👤 Hande Karahan

Overexpression of the low-density lipoprotein receptor (LDLR) is known to decrease apolipoprotein E (APOE) levels and alleviate amyloid beta (Aβ) pathology. We hypothesized that inhibiting the Inducible Degrader of LDLR (IDOL), an enzyme that ubiquitinates LDLR for degradation, would increase endogenous LDLR levels and attenuate amyloid pathology. To investigate the cell-type-specific role of IDOL, we generated Idol conditional knockout mice on an Aβ-amyloidosis mouse model and performed biochemical, histological, and multi-omics analyses. We demonstrated that neuronal, but not microglial, Idol deletion reduced amyloid accumulation and altered brain LDLR and APOE levels, indicating the critical role of neuronal IDOL-LDLR in amyloid pathology. In addition, neuronal Idol deletion increased the levels of Reelin receptors important for synaptic function, and single-nuclei RNA sequencing revealed significant changes associated with synaptic organization. Neuronal IDOL, but not microglial IDOL, plays a key role in Alzheimer's disease pathogenesis by regulating the levels of brain APOE receptors. Neuronal, but not microglial, Idol deletion reduces amyloid burden and modulates brain APOE and LDLR levels. Deletion of neuronal Idol increases the levels of APOER2 and VLDLR, the Reelin receptors, in the brain. Single-nuclei RNA sequencing highlights the neuronal IDOL's impact on inhibitory neurons and synaptic organization. Targeting neuronal IDOL may provide multiple therapeutic benefits in Alzheimer's disease by modulating APOE receptors. Show less

To summarize the nutritional supplementation on biochemical parameters, cognition, function, Alzheimer's Disease (AD) biomarkers and nutritional status. PubMed, Web of Science, Korean Journal Database, Russian Science Citation Index, SciELO Citation Index, Cochrane Library and Scopus databases were searched until 16 April 2021. 22.193 records in total were reached according to inclusion and exclusion criteria. Included Studies were evaluated through the Modified Jadad Scale and gathered under four subheadings. Forty-eight studies with a total of 7009 AD patients were included. Souvenaid, ONS (368 ± 69 kcal), Vegenat-med, 500 mg Resveratrol, ONS (200 mL) were effective nutritional supplements on promoting weight gain and protecting malnutrition status but showed conflicting results in Body mass index, Mid-Upper-Arm Circumference and Triceps Skin Fold Thickness. ONS and a lyophilized whole supplementation Vegenat-med intake made an increase in MNA scores. While all nutritional supplements showed controversial results in biochemical parameters but caused a decrease in Hcy levels which caused reductions in brain Aβ plaque (increase serum Aβ), p-Tau and cognitive improvement. Folic acid and vitamin D decreased serum APP, BACE1, BACE1mRNA. Resveratrol, Better designed trials with holistic measures are needed to investigate the effect of nutritional support on the AD biomarkers, cognitive status, biochemical parameters and functional states. Also, more beneficial results can be obtained by examining the simultaneous effects of nutritional supplements with larger sample groups. Show less