11549 RESULTS
COMMENT Merrill et al. uncover the remarkable heterogeneity and brain-specific nature of lipoprotein particles (Lps) in the cerebrospinal fluid (CSF) of the human brain. To date, such CSF-Lps have remained understudied in comparison to the analogous lipoprotein p
COMMENT This very interesting study focuses on human CSF functional lipoproteins by identifying novel proteins and networks specific to CSF that are involved in multiple CNS diseases. Especially novel is the experimental design of lipid size-based isolation, foll
COMMENT This work describing the diversity of human CSF lipoprotein species is timely and likely to have a strong impact on the field of Alzheimer’s disease. Previous elegant, yet perhaps underappreciated, studies have described differences in CSF particles in AD
COMMENT The study of plasma lipoproteins is a field unto itself, with decades of work profiling the variety, heterogeneity, protein/lipid content, and risk profile of these peripheral particles. When it comes to the brain, previous work by Weisgraber, Mahley, Yas
COMMENT Both old and new human genetic findings strongly implicate lipoprotein metabolism in the etiology of AD. For example, apolipoprotein genes APOE and CLU/APOJ, and ABC transporter genes ABCA1 and ABCA7, which load lipids onto apolipoproteins to produce lipo
COMMENT Merrill et al. report a treasure drove of biochemical information on the protein composition of cognitively normal human donor CSF and the size profile of lipid-containing constituents (lipoprotein particles and extracellular vesicles) of CSF. Of particul
COMMENT This work represents a significant advancement in our understanding of which proteins are present in human CSF lipoprotein particles, the brain's counterpart to LDL and HDL. Yesterday, there were a mere dozen or so proteins identified; today, that nu
COMMENT Recent breakthroughs in Alzheimer's research have provided insight into a complex interplay between lipids, glial cells, and neurodegeneration, offering hope for innovative therapeutic strategies. The two studies discussed here play a pivotal role in
COMMENT In this study, the authors developed a three-dimensional human neuroimmune axis model, which includes human stem-cell-derived neurons, astrocytes, and microglia, together with human peripheral immune cells, to model AD pathology and progression. They foun
COMMENT Intraneuronal aggregates of α-synuclein (αSyn) are the hallmark of pathology in Lewy body diseases (LBD), including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) (Henderson et al., 2019). Diffuse cortical spread of αSyn pathology correlates
COMMENT Both studies, by Prakash et al. and Haney et al., found lipid droplet (LD)-rich microglia around Aβ plaques in relevant brain regions of AD, which impacts microglia function. Their studies suggest to the authors that reducing LD formation is a strategy to
COMMENT As an ApoE 4 homozygote, who discovered her genetic status though a NIH-funded study without counseling and experienced the following PTSD and suicide ideation that almost ended my life, I find this horrific. I can buy this test with little oversight. Whe
COMMENT These two papers support accumulating literature reporting dysregulation of microglial lipid metabolism in Alzheimer’s disease human brain and mouse models. Prakash et al. showed LD formation in microglia in response to Aβ and corresponding increases in L
COMMENT These interesting reports are a step forward. They suggest a functional link between ApoE and Aβ on the one hand, and phospho-tau, perhaps mediated by microglia-derived lipid droplets (LDs). It is possible that the light microscopic observation by Prakash
COMMENT My lab has had a continued interest in the cell-type-dependent impact of APOE4 expression across the brain, particularly as it relates to lipid metabolism in glia. We have previously created isogenic iPSC lines bearing either the disease-neutral allele AP
