9157 RESULTS
COMMENT I was interested in this finding, showing that polygenic risk for AD is associated with a reduction in hippocampal volume throughout the lifespan. The most salient observation of this study is that this small but significant effect is seen in the very ...
COMMENT Single-cell RNA-Seq studies are an incredible resource for the field, but they don’t always represent the full diversity of cell types in the brain. This study from Lau et al. nicely captures an endothelial cell population and adds insight to gene ...
COMMENT The comprehensive comparison of aggregate-selective α-synuclein antibodies by Kumar et al. has been published after the preprint version earlier was published on BioRxiv. The field’s responses are positive—but then what? I think the title of this Alzforum ...
COMMENT Endosomal trafficking dysfunction is a recognized pathogenic hub in Alzheimer’s disease. This elegant study provides further evidence for this, using two model systems, hiPSC-derived astrocytes and Baker’s yeast. Using isogenic APOE e3 and e4 human ...
COMMENT Narayan and colleagues integrate experiments in human astrocytes and yeast models to advance our understanding of endocytic perturbations in Alzheimer’s disease (AD). Based on human genome-wide association studies, a preponderance of AD candidate ...
COMMENT This paper elegantly combines two different techniques to discover that the AD risk gene PICALM modulates the AD-risk gene APOE4. The paper has a signature from two outstanding labs, combining yeast genetic assays (developed in the late Susan Lindquist’s ...
COMMENT Narayan et al. provide evidence of APOE4-induced perturbation to endocytosis in iPSC-derived astrocytes. This APOE4-mediated endocytic dysfunction results from a toxic gain of function of the APOE4 isoform and is cell-type-specific. They also performed ...
COMMENT Neuronal early endosome swelling and proliferation, among the earliest specific signs of AD, are linked to multiple downstream pathophysiological consequences (Nixon 2017; Pensalfini et al., 2020) and are driven by APP-dependent and-independent mechanisms ...
COMMENT This paper very interestingly reports APOE4-dependent endocytosis defects in astrocytes that can be rescued by CALM overexpression. The use of isogenic cultures of APOE4 astrocytes enabled the controlled analysis of endosomal Rabs, transferrin, and EGF ...
COMMENT This is a very nice study. It is the largest GWAS in African Americans so far, though it is far below the sample size of the genetic studies from Europeans, which included almost 100,000 individuals. This study suggests that it is possible additional ...
COMMENT This is a tour de force assessment of different antibodies previously reported to be specific for certain types of α-synuclein aggregate. They are not! I commend the authors for this thorough, systematic, honest, and self-critical approach to preparing ...
COMMENT The study from Kumar and colleagues is an important contribution to the field. It attempts to bring some consensus on the validity and characterization of these commonly used "conformation-specific" antibodies. Characterizing and validating ...
COMMENT Characterizing the transcriptomic changes of AD patient brains at the single-cell level enables the identification of cell-type-specific dysregulated pathways in AD. While single-nucleus RNA-sequencing (snRNA-Seq) allows examining the transcriptomic ...
COMMENT Few questions have led to more confusion than that of the relative importance of oligomers and filaments. Part of the problem stems from the fact that filaments are easily observed in human brain, whereas oligomers are largely invisible. It would ...
COMMENT Kumar and colleagues set out in their study to characterize a variety of available ‘conformation- specific antibodies’ for α-Syn to test the antibodies’ specificity toward monomeric, oligomeric and fibrillar forms of α-Syn. The results largely agree with ...
