15 RESULTS
COMMENT Mary Jo was a constant in the field of APOE and Alzheimer's disease from the very beginning. She brought an expertise in lipid biology to the questions of neurodegeneration related to APOE. Over her nearly 30 years in the field, she organized many of
COMMENT This study is a dramatic demonstration of APOE characteristics that promote neurodegeneration, greatly clarifying the more general models of APOE-related risk. In convincing ways, it pushes forward ideas from disparate studies to demonstrate that APOE lip
COMMENT This work greatly builds the literature of amyloid-independent effects of APOE4 in AD pathogenesis. Using diverse imaging and CSF analyses, Montagne et al. show that blood-brain barrier (BBB) leakage in humans is more pronounced in APOE4 individuals with
COMMENT This is clearly an important study. However, prevention in an epidemiology study is likely delay of initial pathology, whereas prevention in this type of study would likely be delay of symptoms arising from existing pathology. Thus, this negative NSAID fi
COMMENT The work identifies a mechanism for the known anti-inflammatory effects of ApoE through a series of approaches. The authors demonstrate that ApoE’s high-affinity binding to the C1q protein inhibits the classical complement cascade, a clear example of a di
COMMENT Surprisingly, the effects of sex on ApoE4-related risk of Alzheimer's disease have not been well examined. The studies most referenced are from the 1990s, despite the huge growth in information about ApoE genotype and AD since then. Now, in a meta-an
COMMENT The work of Huang et al. is very interesting in its finding that one of the mechanisms of ApoE altering Alzheimer’s disease risk is through neuronal signal transduction, involving DLK, ERK, and cFos. The data show that the three ApoE isoforms differential
COMMENT This work from Dudley Strickland's lab describes a new protein related to the LDL receptor family, termed LRAD3. This protein shares structural similarities to other members of the family, including domains for the internalization and sorting of (as
COMMENT This paper provides really compelling data that one role of ApoE in AD pathogenesis is by promoting Aβ clearance. One strength of the work is that the authors use in-vivo systems to assess what is happening to the Aβ produced in the brain. The conclusion
COMMENT Zhang et al. have published a very interesting study showing that deletion of the striatal-enriched tyrosine phosphatase (STEP) gene protects the 3xTg animal model of Alzheimer disease. The interesting part of this study is that the protection is not at t
COMMENT Comment on Herz et al. This work addresses an exciting target in therapeutic approaches against
COMMENT The last time I saw Anne, I stopped by unannounced in her lab at McLean. She was talking to someone from her lab, and she kindly introduced me to him, and then asked him to leave so we could talk, which we did for two hours. Seeing Anne was like coming ho
COMMENT Several groups have found that X11 and X11L1 interact with APP, affect APP metabolism, and decrease the production of Aβ. However, a recent study found that X11 siRNA and X11L siRNA treatment did not alter the levels of α-CTF and β-CTF, but decreased Aβ.
COMMENT LXR¹s are nuclear hormone receptors that bind to hydroxylated forms of cholesterol and promote transcription of genes involved in lipid homeostasis (e.g., ApoE, ABCA1). Cholesterol homeostasis is poorly understood in the brain, but of obvious importance b
COMMENT Over the last 10 years, numerous studies have indicated that the low-density lipoprotein receptor-related protein (LRP) may be important for the pathogenesis of Alzheimer's disease. These include studies showing that LRP can internalize membrane-boun
