151 RESULTS
COMMENT The Phase 2 donanemab results are exciting and important. This innovative trial of a highly potent amyloid-normalizing antibody met its primary cognitive/functional endpoint. As with other such antibodies, a significant number of participants developed AR
COMMENT In any therapeutic trial, of course it is much nicer to detect a potential signal of efficacy than not to detect such a signal. The more limited that signal is, though, the more cautious we have to be in interpreting its basis. One possibility here is tha
COMMENT This study used a straightforward trial design with a clear outcome, which met the prespecified outcomes. The rate of amyloid-related imaging abnormalities was not trivial but the consequences were manageable. The effect size of reduction of decline was s
COMMENT Saturday was a very exciting day! The donanemab Phase 2 study offers some of the most compelling evidence to date that amyloid reduction can slow clinical decline, albeit modestly, in early stages of AD. While we have seen a suggestion of similar results
COMMENT I am very encouraged. This trial met its prespecified primary endpoint, which I believe is a first for an anti-amyloid drug in our field. In addition, the growth of tau, measured by tau PET in the frontal lobes, was slowed; this provides evidence of disea
COMMENT Checler et al. have published a very informative review of the evidence that the precursor to Aβ, the “βCTF” or “C99” fragment of APP, is likely a very important (if not the most important) derivative of APP acting in the pathogenic process leading to Alz
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 th
COMMENT This study sheds more light on the role of ApoE in the brain. It is known that ApoE activates a range of growth-factor like receptors and plays a role in lipid metabolism (Liu et al., 2015; Zhao et al., 2017). APOE4 appears to be less able to activate th
COMMENT The work by Sienski and colleagues, demonstrating the perturbation of lipid homeostasis by APOE4, is of much interest because it suggests another pathway by which APOE polymorphisms may increase susceptibility to Alzheimer’s disease. In particular, the au
COMMENT TMEM106B first came under the scientific spotlight as a risk gene for frontotemporal lobar degeneration-TDP-43 (FTLD-TDP) (Van Deerlin et al., 2010), but the gene’s clinical implication goes beyond TDP-43 proteinopathy. A common TMEM106B haplotype tagged
COMMENT Variants in TMEM106B, coding for a lysosomal transmembrane protein, were recognized as important genetic modifiers in different neurodegenerative diseases and, in particular, in FTD patients harboring GRN mutations. Now, TMEM106B comes into the spotlight
COMMENT The authors developed a very valuable model to connect cortical inflammation, cortical circuit activity, and the loss of dendritic spines. Specifically, this effect is transient. When the inflammation receded, synaptic connectivity recovered, and cortical
COMMENT This study by Wilmanski et al. provides strong additional support for the idea that alterations in, distinct signatures of, and taxonomic diversity and abundance within the gut microbiome play important roles in physiological versus pathological aging, an
COMMENT Fred, during his master's biology at the Free University Amsterdam, was a trainee at the Netherlands Institute for Brain Research in Amsterdam, an institute of the Royal Netherlands Academy of Arts and Sciences. In 1975 he was appointed in the neuroe
COMMENT A polygenic test for measurement of Alzheimer's risk will be valuable when a disease-modifying therapy is available. At the current moment I am skeptical of its value. Healthy lifestyle behaviors are advisable for all people regardless of genetic ris
