11526 RESULTS
COMMENT This work represents another tour de force from the Goedert and Scheres groups. They have allowed a tau fragment to spontaneously fibrillize under different conditions, which lead either to a conformation that mimics that found in Alzheimer’s disease, or,
COMMENT We discovered about 15 years ago that IL-17, a key T-cell-derived cytokine, contributes to hypertension. Subsequently, others confirmed this. Hypertension is clearly associated with cognitive dysfunction. Indeed, this group has made an enormous contributi
COMMENT This elegant study nicely demonstrates that neurovascular and cognitive dysfunction associated with salt-sensitive hypertension is mediated by two distinct mechanisms, involving IL-17 acting on cerebral endothelium and on parenchymal border (perivascular
COMMENT This is an interesting, in-vitro study with recombinant tau (297–391), analyzing structures of intermediate amyloid species that form during the assembly into filaments containing the Alzheimer or CTE fold, leading to a model in which prefibrillar, oligom
COMMENT Reading this paper from the laboratories of Michel Goedert and Sjors Scheres at the MRC in Cambridge, U.K., is like opening a box of chocolates for the holidays and finding a delightful assortment of shapes and structures: treats as food for thought. I ha
COMMENT Another advance from the Scheres/Goedert collaboration and in vitro filament wizard Sofia Lövestam. The first intermediate filaments (FIAs) seen have a short-ordered core, with presumably the lowest activation energy barrier. Soon thereafter, stabler conf
COMMENT This study employs unbiased clustering of over 400 CSF proteomic profiles to categorize or subtype distinct groups of individuals clinically diagnosed with AD. This type of unbiased classification is important because, despite displaying indications of de
COMMENT Alzheimer’s disease is molecularly highly heterogeneous, involving many different pathophysiological processes. This heterogeneity may also contribute to the limited effects observed in current clinical Alzheimer’s disease (AD) trials, highlighting the ne
COMMENT This is undoubtedly a step forward in the molecular characterization of AD, which, in concert with pathological and imaging studies, indicates that the molecular drivers are diverse, even though amyloid and tau may be frequent downstream offenders. The fi
COMMENT The evaluation of cognitive tests for their predictive abilities requires, and seems to routinely receive, close attention to the testing context. Subjects are all familiar enough with the computing device to rule out computer sophistication effects, espe
COMMENT There is a complex relationship between lipid metabolism and AD pathophysiology. ApoE is a major genetic risk factor for late-onset AD and the major lipid carrier in the central nervous system. In the brain, apoE also mediates the removal of cholesterol i
COMMENT This article presents the therapeutic effects of the LXR ligand GW3965 in 9.5-month-old tau transgenic mice expressing human E3 (TE3) or E4 (TE4) as well as their E3 and E4 non-transgenic controls. The authors evaluated several parameters indicative of ne
COMMENT This is a thought-provoking study by my colleagues at BWH. Moors et al. build on the lab’s previous insight into how female sex may protect from α-synuclein pathology. Digging deeper into the mechanism(s), this paper identifies estrogen-receptor α as a ke
COMMENT This is elegant work by my colleagues Silke Nuber, Tim Moors, and team. It combines sexual dimorphism and protein palmitoylation to reinforce the view that synaptic dysfunction is one of the key drivers of early synuclein pathology. While the results are
COMMENT This publication builds on Silke Nuber’s work on sex differences in PD in vivo models (Rajsombath et al., 2019), and that of Dennis Selkoe and Gary Ho on palmitoylation modifying αS PD phenotypes including neurotoxicity and αS accumulation (Ho et al., 202
