Tim Viney on Early and selective localization of tau filaments to glutamatergic subcellular domains within the human anterodorsal thalamus.

COMMENT hope that the Alzforum community finds these results informative, and welcome replies to this comment

Erik Musiek on Donanemab Approval Likely to Pose New Quandaries for Clinicians

COMMENT I am pleased to hear the positive news on donanemab and agree that it is likely to be approved soon. Donanemab has some potential advantages over lecanemab, but also may have some weaknesses, so it will be nice for clinicians to have both as options. Cert

Stephen Salloway on Donanemab Approval Likely to Pose New Quandaries for Clinicians

COMMENT The FDA Advisory Committee’s unanimous recommendation that donanemab receive full approval represents an important step forward in the treatment of Alzheimer’s disease. ARIA, the principal adverse event, is usually transient, asymptomatic, and manageable

Gil Rabinovici on Donanemab Approval Likely to Pose New Quandaries for Clinicians

COMMENT I commend the FDA PCNS Advisory Committee on a very thoughtful discussion today. I completely agree with the committee’s favorable conclusions regarding donanemab’s efficacy and risk/benefit profile. I also agree that the innovative and forward-thinking t

Eric Siemers on Donanemab Approval Likely to Pose New Quandaries for Clinicians

COMMENT The FDA advisory committee meeting held on June 10 for donanemab was another important advance for patients, families, and the field. Using the iADRS as the primary outcome variable, and the CDR-SB as a key secondary, the committee unanimously voted 11- 0

Lon S. Schneider on Donanemab Approval Likely to Pose New Quandaries for Clinicians

COMMENT The Perfect Meeting Three years ago, an FDA adviser called the agency’s approval of Aduhelm “probably the worst drug approval decision in recent U.S. history.” By contrast, a current adviser called today’s donanemab session “a perfect meeting.” FDA got th

Behrooz Yousefi on New PET Ligand Captures α-Synuclein in Parkinson’s, MSA Brains

COMMENT The in vivo detection of α-synucleinopathies represents a significant unmet need, and it is a highly challenging area of research. Several groups have been developing small molecules that could be utilized as positron emission tomography (PET) tracers for

Oskar Hansson on New PET Ligand Captures α-Synuclein in Parkinson’s, MSA Brains

COMMENT I applaud researchers who are developing new potential PET tracers for α-synuclein diseases, because the need is imperative, especially for use in studies determining target engagement of new drugs targeting misfolded α-synuclein. However, it is a challen

Harald Steiner on Caught in the Act: Cryo-EM Exposes γ-Secretase Catalytic Pose

COMMENT This is beautiful work. The question of whether the mechanism—the formation of a stabilizing hybrid β-sheet that allows unwinding of the preceding small part of the transmembrane helix to expose the cleavage sites—would also be seen for the subsequent ste

Per Kristian Eide on CSF Hugs Arteries to Squeeze into the Brain

COMMENT We thank Dr. Sarmad Peymaei for his comments on our article. The article includes a number of

Michael Greicius on Unanimous: FDA Advisory Committee Backs Donanemab

COMMENT Fundamental questions about the efficacy of donanemab (and also lecanemab) remain. It is remarkable that we have not seen a scatterplot showing the association between amyloid reduction and cognitive outcomes in the donanemab or lecanemab studies. The pro

David Knopman on Unanimous: FDA Advisory Committee Backs Donanemab

COMMENT have required PET scanning, they could have emphasized in their comments that donanemab administration

Wenjie Luo on Microglia Make Tau, Spelling Their Demise in Tauopathies

COMMENT Our current understanding is that tau, encoded by the MAPT gene, is highly enriched in neuronal axons and present at minimal levels in non-neuronal cells. However, in the brains of individuals with FTLD-tau, those inclusions have been detected in glial ce

Kiran Bhaskar, Jonathan Hulse, Karthikeyan Tangavelou on Microglia Make Tau, Spelling Their Demise in Tauopathies

COMMENT Microtubule-associated protein tau traditionally has been viewed solely as a neuronal protein, pivotal in the progression of neurodegenerative conditions such as Alzheimer’s disease and primary tauopathies. Consequently, our focus has predominantly center

Kristine Freude on Microglia Make Tau, Spelling Their Demise in Tauopathies

COMMENT Iyer et al. present compelling evidence of MAPT expression and presence of endogenous tau in microglia (iMGLs), utilizing both human brain samples and induced microglia-like cells derived from induced pluripotent stem cells (iPSCs). This finding is signif