11527 RESULTS
COMMENT The manuscript from Lucia Chavez-Guttierez and colleagues may prove to be a milestone in the reconciliation of the idea that Aβ is the pathological agent driving Alzheimer’s disease and the alternative view that, instead, APP’s βCTF is critical for the di
COMMENT resolving the debate regarding FAD pathogenesis in this comment (Wolfe, 2015). The (FAD-linked)
COMMENT This is an interesting follow-up study to Szaruga et al., 2017, from the Chávez-Gutiérrez lab, in which it was first suggested that FAD mutations lead to destabilization of γ-secretase-C99 enzyme-substrate (E-S) complexes. However, neither the present EMB
COMMENT Zoltowska et al. propose that Aβ42 inhibition of γ-secretase is the principal basis for lysosome dysfunction and the rise of APP-βCTF levels seen in AD brain. We welcome their appreciation of APP-βCTF’s pathogenic potential in AD and the new investigation
COMMENT This work describes a well-designed series of studies testing the hypothesis that the pathological accumulation of Aβ1-42 competes with other substrates for γ-secretase processing, resulting in the accumulation of unprocessed γ-secretase substrates, inclu
COMMENT Good science is built on replication and validation. This new paper makes an importation contribution to both. It is unclear why the heritability of PSP is so low, in contrast to the closely related disorders of frontotemporal dementia. This is good news
COMMENT When considering the causes of AD development, it should be taken into account that this disease occurs not only due to impaired metabolism of Aβ and tau protein in the cerebral tissue and vascular wall, but also because of specific disorders of cerebral
COMMENT Using low-intensity ultrasound to deliver anti-Aβ antibodies to the brain is indeed a promising strategy to increase antibody levels in the brain (and reduce ARIA). We have shown previously that ultrasound achieves a fivefold increased brain uptake of an
COMMENT These are promising exploratory findings that will hopefully be confirmed and extended in the larger ongoing trial. Collectively, this data, in light of some of the failed tau antibody trials, supports our view that targeting intracellular tau is likely t
COMMENT The take-home message of this interesting study is that the RhoA/ROCK/GSK3β pathway appears to be an important regulator of tau phosphorylation, and that this pathway can be modulated by sTREM2. In a therapeutic approach, the authors designed a small pept
COMMENT This very important study emphasizes the danger of equating WMH with systemic vascular risk in older persons. It also highlights cerebral amyloid angiopathy as an important factor in the evolution of WMH, and that WMHs may appear before the evolution of i
COMMENT I am delighted to see that consideration of the role and meaning of white-matter hyperintensities (WMH) continues to be part of our conversation about Alzheimer’s disease. The paper by Shirzadi and colleagues showcases the powerful approach of combining d
COMMENT Another clue is revealed in the mystery of soluble TREM2, unraveling its receptor as well as its function, and surprisingly, in neurons! The authors further explored the function of sTREM2 on neurons, which was observed in the 5xFAD mouse model of cerebra
COMMENT The hallmarks of AD pathology are neurodegeneration associated with tau and Aβ pathologies. Studies in cultured cells and animal models reported over many years have indicated that each one of these three lesions can lead to one of the other two, creating
COMMENT The biology of soluble TREM2 (sTREM2), shed from activated microglial cells from its precursor TREM2, is a focus of AD research because TREM2-activating antibodies, which are used in clinical studies, bind and stabilize sTREM2 in the brain of AD mouse mod
