109 RESULTS
COMMENT Tau is increasingly looking more like a sensitive but nonspecific biomarker of neuronal injury than a causative agent. Is it time for a paradigm shift? marcia_124021 0
COMMENT This is a very important paper, showing the unexpected result that semagacestat causes the accumulation of longer Aβ species and short peptide byproducts that are produced by the sequential carboxy-terminal trimming activity of γ-secretase. The paper high
COMMENT There is firm evidence from experimental studies and observations on human brains with Alzheimer’s disease that cerebral amyloid angiopathy is a consequence of a failure of clearance of Aβ and interstitial fluid from the brain. In order to test new therap
COMMENT This is a very interesting study lending additional support for the hypothesis that increased intracellular Aβ is a major culprit of neurodegeneration and cognitive decline, while extracellular pool of Aβ plays relatively minor role. One obvious conclusio
COMMENT Based on the observations that semagacestat inhibited only secreted Aβ but not intracellular or Aβ byproducts, Tagami, et al. suggested that semagacestat is only a “pseudo” γ-secretase inhibitor (GSI). However, an obvious alternative interpretation of the
COMMENT This is a comprehensive study that further shows the complexity of the processing of APP and Aβ. The authors have used several different cell lines and a mouse model to show that the γ-secretase inhibitor (GSI) semagacestat may not act as previously belie
COMMENT This paper in Cell Reports is a wake-up call for the field. It should revive interest in the γ-secretases, a field in Alzheimer’s research that got a severe blow some years ago when the failure of the semagacestat trial was announced (Doody et al., 2013).
COMMENT The Nobel Prize for cryo-electron microscopy honors the development of and recent breakthroughs that have been achieved by this extremely powerful structural biology technique. Currently there is hardly a week in which an exciting cryo-EM structure of a c
COMMENT The paper by Buckley et al. shows that higher subjective cognitive decline (SCD) scores are associated with higher tau burden in the brain in clinically healthy older adults. However, this finding does not yet justify considering SCD as an indicator for t
COMMENT Due to inconsistent results, it is still under debate whether subjective cognitive decline (SCD) represents an early sign of Alzheimer’s disease. Previous evidence showed that SCD was associated with future objective cognitive decline and conversion from
COMMENT Network hyperexcitability leading to rhythm disturbances in cortical and hippocampal microcircuits is a feature of many neurodegenerative disorders at some stage during their progressive course, and tau is a key switch in the appearance of abnormal inform
COMMENT This paper from the Ittner group is quite interesting, and primarily documents a novel "noncanonical" function of tau, i.e., a tau-dependent activation of the ERK pathway. The findings are in line with previous findings of this team (and others)
COMMENT I don’t know how bioavailable the boron compounds will be in the CNS, but the safety profile associated with targeting NLRP3 should be quite good. There are currently five companies that have been formed to make NLRP3 inhibitors, in the hope of getting th
COMMENT This is an interesting paper. There are several reasons why there might be a sex difference in the relationship between midlife hypertension and risk of dementia, i.e., higher rates in women. First, the paper purports to document that their method of asce
COMMENT The paper by Zhao et al. and other earlier findings have shown that ApoE4 impairs neuronal insulin signaling. In the current paper, the authors showed both recombinant ApoE3 and ApoE4 can bind to the insulin receptor, with ApoE4 having higher affinity. Bu
