47 RESULTS
COMMENT As evidence grows for the importance of early intervention in Alzheimer's disease, an understanding of the initial pathogenic processes is essential. Michno and colleagues present iSILK as an auspicious method for following the development and ...
COMMENT Few scientists in the Alzheimer's field would disagree that we need an animal model that more faithfully manifests the disease as it occurs in humans. Genetically modified mice have been a boon to studies of cellular and molecular mechanisms, but ...
COMMENT Having speed-read the tau controversy, I would conclude that the findings of the Mandelkow group are reasonable within the context of their experimental conditions. The problem is one of comparing apples and oranges, as pointed out by Diamond et al. The ...
COMMENT This new report from the MRC Laboratory of Molecular Biology is yet another fascinating look at the molecular heterogeneity of polymeric tau. Tauopathy occurs in more than 20 different brain diseases (Spillantini et al., 2013), and thus may be the most ...
COMMENT Cryo-electron microscopy (cryo-EM, aka electron cryomicroscopy) has become the go-to tool for determining the molecular architecture of alternatively folded proteins in various disease states. A particular advantage of cryo-EM is that it can be applied to ...
COMMENT I met Dale around 25 years ago, when the Alzheimer’s field was in an uncertain state. Researchers were seeking a clear path to disease modification, but many of the tools that would make this possible were still lacking. Dale and I began a brief and ...
COMMENT Beginning in the 1980s, experiments have shown that prions injected into the eye translocate with high spatial and temporal specificity to downstream components of the visual system (Buyukmihci et al., 1983; Fraser, 1982; Kimberlin et al., 1986; Liberski ...
COMMENT This certainly is an important and thoughtful commentary that keeps us focused on unanswered questions. However, I would take issue with the statement that “the molecular mechanisms of PrP proliferation and neurotoxicity in ‘classical’ prion diseases are ...
COMMENT I think this strategy has considerable value for clarifying how pathogenic protein molecules interact to cause disease. A key question, though, is where the proteins interact in the cell, since this could strongly influence the outcome. For instance, the ...
COMMENT The study by Yetman and colleagues is nicely done, and the resolution of the images is superb. The authors convincingly show that the “leakage” of transgene expression in the Nop-tTA driver line is much more extensive than was previously thought. The ...
COMMENT This is an elegant series of experiments using interesting and informative models. The findings complement a growing literature demonstrating the cell-to-cell spread of pathogenic protein seeds formed by Aβ, PrP, tau, alpha-synuclein, SOD1 and others. ...
COMMENT The prion paradigm has considerable explanatory power for the ontogeny of human neurodegenerative diseases, which mostly appear to emerge from the endogenous misfolding and seeded aggregation of disease-specific proteins. These two papers add to ...
COMMENT These thorough and elegant studies are the strongest evidence yet that seeds of tau protein behave like prions. They compellingly reinforce the prion concept as one of the most important pathogenic principles of our time. But since a prion is defined as ...
COMMENT The data in this study look convincing, and send the encouraging message that tauopathy, an intracellular proteopathy, can indeed be mitigated by an agent that appears to intercept seeds extracellularly. Hence, it may not be necessary for therapeutic ...
COMMENT This paper by Wang et al. is well written and makes a strong case for potentially reversible declines in neuronal function with age. As the authors note, despite their relatively close biological proximity to humans, rhesus monkeys do not develop ...
