26 RESULTS
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COMMENT We are at a critical juncture for BACE1 inhibition research. The disappointing results of the recent BACE1 inhibitor clinical trials is giving way to the sentiment that BACE1 is too risky a therapeutic target to pursue for AD. This feeling is understandab
COMMENT I agree with Paul Aisen’s remarks. The evidence that Aβ is a key initiator of AD is overwhelming, and BACE inhibition early in the disease process should therefore prevent AD. However, BACE has many substrates that perform important functions in the brain
COMMENT I found it very interesting that Eisai did not observe the cognitive worsening that other BACE1 inhibitors have reported. Given that the majority of the other BACE1 inhibitors exhibited the cognitive worsening side effect, I originally concluded the decli
COMMENT Stefan Lichtenthaler gave an outstanding talk at AD/PD 2021. He presented very compelling mass spectrometry data that GP130 is a robust BACE1 substrate. It will be interesting to see what role this new BACE1 substrate may have regarding the cognitive wors
COMMENT The approval of aducanumab, although controversial, may open new opportunities in the areas of prevention and combination trials for AD. Prevention trials administering aducanumab to asymptomatic, amyloid-positive individuals should move forward. For a co
COMMENT Bart De Strooper's thoughtful and cogent comments provide compelling guidance for the AD field moving forward in our new landscape following the approval of aducanumab. I agree with Bart that the approval of aducanumab will offer new opportunities to
COMMENT This new, interesting mutation offers yet additional compelling evidence in favor of the amyloid cascade hypothesis. Interestingly, the Uppsala APP mutation seems to cause AD by both increasing BACE1 cleavage of APP to generate more Aβ, but it also alters
COMMENT This is an interesting technology with the potential for deep interrogation of protein content in synapses and how they change with age or disease. It would be interesting to see if the technology could be adapted to interrogate other parts of the neuron,
COMMENT This is a useful model to add to the armamentarium of mice to investigate amyloid pathology. It will be particularly useful for testing dose-response relationships of BACE1 inhibitors in vivo. The Swedish mutation makes APP such a strong substrate for BAC
COMMENT The approach is interesting and may provide insights into synaptosome characteristics that reflect synaptic function. Many mRNAs translated in the synaptic spine, such as neurotransmitter receptors, are important for post-synaptic function and regulation.
COMMENT This is an interesting finding that reveals further clues about the interplay between Aβ, BACE1, and tau. The use of in vivo two-photon imaging in APP/PS1 mice either with or without tau is a powerful technique that allows individual plaques to be tracked
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