44 RESULTS
COMMENT Where’s Wally? The avalanche of cryo-EM studies in neurodegenerative diseases continues. This latest offering from the Goedert laboratory highlights the S-shaped protofilament fold in Aβ extracted from human brain tissue. The method of extraction appears
COMMENT The development of biofluid and/or imaging markers for algorithms predicting cognitive decline and disease progression is high on all of our radar screens at the moment. This paper is based on cross-sectional, not longitudinal, CSF biomarkers, with relati
COMMENT Utilizing extensive proteomic data of Aβ plaques from AD patients and multiple sequence alignments, this sound work produced a library of peptides that modify Aβ assembly kinetics, fibril morphology, and deposition pattern, all in vitro. Proteomic analysi
COMMENT This paper is a most welcome contribution to the critically important goal of developing prognostic algorithms for predicting time of onset of symptoms of AD. The authors use a reasonable number (n = 236) of subjects from the longitudinal cohort of the Kn
COMMENT This Uppsala deletion is entirely consistent with the general theory that Aβ accumulation causes AD, and that Aβ drives tau aggregation. As we enter the era of disease-modifying therapies, the pathogenic mechanisms revealed in this study reinforce the nee
COMMENT I was mightily encouraged by the data presented by Lilly and Eisai, which gave further support for the FDA assertion that there was a “reasonable likelihood” that lowering the Aβ-load would result in clinical benefit. For those with “normalization” of Aβ-
COMMENT When, in 1937, John Steinbeck wrote Of Mice and Men, he was drawing on the words of Robert Burns that, “The best laid schemes o' mice an' men/Gang aft a-gley.” In this context, the natural history of Aβ amyloid plaques over 10 weeks in transgeni
COMMENT It is too early to see how this will play out in Australia. Generally our TGA takes more note of what the FDA does than what the EMA does. I believe the FDA decision was fair, balanced, and appropriate given the scientific evidence. I admit to bias, havin
COMMENT David Allsop (1954- 2021) David Allsop was a pioneer in the modern era of Alzheimer’s disease molecular pathogenesis. Mentored by Michael Landon (biochemist) and Michael Kidd (human morphologist, electron microscopist) at the Queen’s Medical Centre, Unive
COMMENT To date, I’m not convinced by any of the experimental or clinical evidence that a conventional virus underlies the pathogenesis of AD. Latent or temperate conventional viral activity may, however, play a role in the relatively common phenocopy of AD, mark
COMMENT The BACE 1 inhibitors are a powerful and specific class of drugs. They were used at very high doses, aiming for 70-90 percent inhibition of APP processing (as were the γ-secretase inhibitors). With the benefit of hindsight, we should not be surprised that
COMMENT The paper by Lauwers et al. is a timely reminder of the transmissible properties of amyloid fibrils. This is a story that started in the 1960s with the observations of the systemic amyloid researchers using experimental models of what is now known as AA a
COMMENT Ever since the origin of Aβ was shown to be the result of proteolytic processing of the juxta-membranous and intramembranous domains of a beta-amyloid precursor protein (APP) (Kang et al., 1987), it has been apparent that this phenomenon must reflect some
COMMENT I am disappointed, but not surprised. The trial sizes were very small, and cognitive readouts are notoriously relatively insensitive. The baseline intake was very heterogeneous in terms of cognitive status (CDR ranging from 0 to 1) and the escalation of d
COMMENT Apart from the topological problem (i.e., the cellular compartments in which each of the players exist: e.g., does extracellular PrP ever normally come into direct contact with cytoplasmic α-syn?), the biological relevance of these interactions remains po
