46 RESULTS
COMMENT Twenty-eight years after the first report of an impact of polymorphisms in the apolipoprotein E gene (APOE) on risk for Alzheimer’s disease, there is still no consensus on a mechanistic explanation for this genetic association. Interactions of the ApoE ...
COMMENT This is elegant and intriguing work. As one possible next step, it might be important to determine whether macrophage-like cells derived from circulating monocytes express the same constellation of TAM receptors, and behave in the same manner, toward ...
COMMENT It would be very helpful if the authors, or other ApoE experts, could weigh in on the mechanism(s) by which ApoE secreted from yeast might interact with cellular processes. Does yeast have any surface receptors capable of binding ApoE? Or do we suppose ...
COMMENT It is worth noting that the responses of mice to scrapie forms of PrP are reportedly sex-dependent (Loeuillet et al., 2010). In that case, greater virulence (a shorter incubation period) was observed in females, but it is easy to imagine that the ...
COMMENT Cluster 13 is rather curious. Is there any possibility that scRNA-seq could pick up RNA from cells that microglia have phagocytosed? RNA has the reputation of being exquisitely labile, and I'm sure that's true if your objective is a complete, ...
COMMENT Once again, I feel compelled to point out that TFEB has been connected to APOE genotype in AD. Essentially, compelling evidence indicates that ApoE4 binds (evidently, with higher affinity than ApoE3) to the "CLEAR" enhancers that comprise the ...
COMMENT This is quite intriguing. I wonder if the association might have anything to do with APOE genotype? I'm rather surprised that the study did not include analysis of that variable. ApoE isoforms have been shown to impact personality traits when ...
COMMENT In their article, Konttinen et al. write: "[E]xact mechanisms underlying human APOE4-induced inflammatory phenotype in AD microglia remain incompletely defined." Their study and several other recent publications suggest a strong possibility of a ...
COMMENT Regarding ApoE and autophagy, it appears the mechanism is a surprising one. A few years ago, Dale Bredesen and colleagues strengthened the evidence for ApoE being found intracellularly, in the nucleus and bound to DNA, in fact. As it turns out, the DNA ...
COMMENT This is a tour de force, integrating many sophisticated forms of analysis. In the context of many other indices of neuroinflammation and microglial malactivation, the evidence that these cells participate in AD progression is difficult to refute. ...
COMMENT The link between APOE genotype and autophagy has recently received mechanistic reinforcement. We have demonstrated avid, specific binding of ApoE to DNA elements known as "CLEAR" sites, the cis elements bound by transcription factor EB (TFEB), a ...
COMMENT Interesting and perhaps related: It has been known for some time that extracellular UPS components are present and functional (Sixt et al, 2008), including in cerebrospinal fluid (Mueller et al., 2012). This may reflect favorably on Model 2 proposed by ...
COMMENT This study by Woodruff et al. has provided intriguing new ideas about the roles of enzymes that have previously garnered interest almost exclusively due to their effects on APP. BACE1 and γ-secretase are well-known to have effects on other substrates, and ...
COMMENT There was a really small difference in the exercise levels reported to confer risk. And I take issue with the claim by the paper's authors, and the reporting in this Alzforum article, that patients and controls differed in the number of times per ...
COMMENT Joachim Herz and his lab have accomplished a milestone in research on the biology of reelin, a protein that has complex biochemistry and genetic contributions to brain development, as well as synaptic plasticity in the adult. Because it is so critical for ...
