Masayasu Okochi on Semagacestat, a Pseudo γ-Secretase Inhibitor?
COMMENT First, we would like to thank all the scientists and interviewees who made comments and gave their
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Michel Grothe on Daydreaming Network Serves as Ground Zero for Aβ Deposition
COMMENT Although our methodological approaches were very different, there is a striking agreement between our finding that amyloid-PET scans considered to be "amyloid-negative" according to commonly used criteria can harbor notable regional amyloid sign
Rachel Buckley, Aaron Schultz on Daydreaming Network Serves as Ground Zero for Aβ Deposition
COMMENT The approach of using CSF and PET to identify earlier stages of β-amyloidosis is quite interesting. Understanding where individuals are in the time course of disease is very difficult, particularly in preclinical stages, and the dual CSF/PET Aβ approach t
Betty Tijms on Daydreaming Network Serves as Ground Zero for Aβ Deposition
COMMENT This study by Palmqvist et al. shows in a rigorous way that when amyloid values in CSF are abnormal, it is possible to identify early amyloid increases in a supposedly normal PET image when focusing on specific anatomical areas. A particularly innovative
Xiao-Hong Lu on Scientists Unleash CRISPR on RNA
COMMENT To change the message: RNA editing for neurodegenerative disorders RNA has long been sought as a therapeutic target to provide transient amelioration of disease status without making permeant changes to the genetic markup. The recently reported RNA Editin
Michael Lardelli on Presenilin-1 Targeted Morpholino Induces Cognitive Deficits, Increased Brain Aβ1-42 and Decreased Synaptic Marker PSD-95 in Zebrafish Larvae.
COMMENT Reading the title of this paper might mislead people to think that there is evidence that zebrafish produce a peptide similar to Aβ. However, while there are two “co-orthologues” of the APP gene in zebrafish (appa and appb), Aβ peptides cleaved from the p
Elizabeth Mormino on PET Staging Charts Gradual Course of Amyloid Deposition in Alzheimer’s
COMMENT In this experiment, Grothe and colleagues find evidence for in vivo staging of amyloid based on regional uptake values extracted from florbetapir PET data from the ADNI. To do this, the authors examine regional positivity within the clinically normal samp
Hamed Najafabadi on Estimates of RNA Decay Hint at Destabilization in Alzheimer’s Brains
COMMENT Professor Lukiw raises several concerns that we also share with regard to our analyses, and we have tried to address them to the point that was possible in the paper. Nonetheless, additional experiments and analyses are warranted to fully address these is
Fred van Leeuwen, Mark Verheijen on The landscape of transcription errors in eukaryotic cells.
COMMENT Transcription errors in Alzheimer’s disease Progress in understanding the crucial mechanisms underlying Alzheimer’s disease has been hampered by technical barriers. However, in the past few years many promising technical improvements have appeared, such a
John Ringman on Among the Healthy, a Positive Amyloid Scan Prompts Questions About Risk
COMMENT The only surprising thing to me was that, despite extensive education on the meaning of a positive and negative amyloid scan, only 62 percent of participants appeared to correctly grasp the significance of a positive scan as putting them at an increased r
Richard Caselli on Among the Healthy, a Positive Amyloid Scan Prompts Questions About Risk
COMMENT Overall, I think this addresses an important issue given the rise of molecular imaging. Although the authors reported that the smallest number of responses indicated “imminent” risk or were “diagnostic of” Alzheimer’s, this constituted 12 percent of the s
Michael Schöll on PET Staging Charts Gradual Course of Amyloid Deposition in Alzheimer’s
COMMENT In this staging scheme proposed by the authors, the consistency of the pattern is certainly striking and will be very useful in terms of recruitment into clinical trials and diagnostic prognosis. What strikes me is the discordance between very early pre-s
Samantha Burnham on PET Staging Charts Gradual Course of Amyloid Deposition in Alzheimer’s
COMMENT This is an interesting study by Grothe and colleagues that suggests a typical pattern of regional deposition for neocortical Aβ in AD. Interestingly, the staging criteria they apply to the regional deposition allows for more than 45 percent of older clini
Grace Stutzmann on For Synapses, Are Aβ Oligomers a No-Go?
COMMENT Zhao et al. present an interesting study with a clearly presented mechanism proposing how exogenously applied ADDLs can result in synaptic decline via a reduction in Nogo-regulated spine assembly. This involves an inhibition of the low threshold, low cond
Walter J. Lukiw on Estimates of RNA Decay Hint at Destabilization in Alzheimer’s Brains
COMMENT Alkallas et al. have reported on enhanced mRNA destabilization in aged and female Alzheimer’s disease (AD) brains as the result of downregulation of the “protective” RNA-binding proteins (RBP) RBFOX1 (RBP fox-1 homolog) and ZFP36 (also known as the zinc f