The impact of mild episodic ketosis on microglia and hippocampal long-term depression in 5xFAD mice.

Ketotherapeutics is a potential metabolic intervention for mitigating dementias; however, its mechanisms and optimal methods of application are not well understood. Our previous in vitro study showed that β-hydroxybutyrate (BHB), a major ketone body, reverses pathological features of amyloid-β oligomer (AβO)-activated microglia. Here we tested the in vivo effects of BHB on microglia and synaptic plasticity in the 5xFAD Alzheimer's disease (AD) mouse model.

Unique N-glycosylation signatures in Aβ oligomer-and lipopolysaccharide-activated human iPSC-derived microglia.

Microglia are the immune cells in the central nervous system (CNS) and become pro-inflammatory/activated in Alzheimer's disease (AD). Cell surface glycosylation plays an important role in immune cells; however, the N-glycosylation and glycosphingolipid (GSL) signatures of activated microglia are poorly understood. Here, we study comprehensive combined transcriptomic and glycomic profiles using human induced pluripotent stem cells-derived microglia (hiMG).

Nitroxyl Hybrids with Curcumin and Stilbene Scaffolds Display Potent Antioxidant Activity, Remodel the Amyloid Beta Oligomer, and Reverse Amyloid Beta-Induced Cytotoxicity.

The disorder and heterogeneity of low-molecular-weight amyloid-beta oligomers (AβOs) underlie their participation in multiple modes of cellular dysfunction associated with the etiology of Alzheimer's disease (AD). The lack of specified conformational states in these species complicates efforts to select or design small molecules to targeting discrete pathogenic states. Furthermore, targeting AβOs alone may be therapeutically insufficient, as AD progresses as a multifactorial, self-amplifying cascade.

Effects of Sex and Western Diet on Spatial Lipidomic Profiles for the Hippocampus, Cortex, and Corpus Callosum in Mice Using MALDI MSI.

Diet is inextricably linked to human health and biological functionality. Reduced cognitive function among other health issues has been correlated with a western diet (WD) in mouse models, indicating that increases in neurodegeneration could be fueled in part by a poor diet. In this study, we use matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) to spatially map the lipidomic profiles of male and female mice that were fed a high-fat, high-sucrose WD for a period of 7 weeks.