11505 RESULTS
COMMENT I commend the authors for their multimodal imaging approach to brain age estimation. Making use of 1705 imaging-derived phenotypes as parameters for estimating brain age, this study used information from T1- and T2-weighted structural MRI, functional MRI,
COMMENT In this study, Western et al. leveraged CSF-based proteomics via the SOMAscan 7k platform and genetic data from approximately 3,500 individuals to conduct the largest investigation of CSF protein quantitative trait loci (pQTLs) to date. This study provide
COMMENT This study presents a comprehensive analysis of transcriptomic changes in astrocytes across different parts of the neural network vulnerable to Alzheimer’s disease. Using single-nucleus RNA sequencing, the authors analyzed 628,943 astrocytes from 32 donor
COMMENT The work led by Swarup, Miyoshi, and Head is a tour de force and a valuable contribution of incredibly rich datasets to the field. The design is strong with comparisons between early stage AD and late-stage AD and Down’s syndrome to derive shared and spec
COMMENT I think the proposal by Aisen and colleagues for approval of antibodies that remove Aβ based solely on imaging and supportive biomarker evidence is premature. While there is evidence from interventional and observational studies in support of an “amyloid
COMMENT The International Working Group has long contributed to refining the definition and diagnosis of Alzheimer’s disease (Dubois et al., 2007, 2024). Among its many efforts, two contributions remain essential: 1) In clinical practice, AD should be diagnosed o
COMMENT The authors present a case for accelerated regulatory approval of amyloid-lowering immunotherapies. Given current data in the field from anti-amyloid immunotherapies, they make several key points regarding anti-amyloid antibodies: Evidence of robust amylo
COMMENT The authors state that lowering amyloid plaques, or attenuating their increase compared to placebo, should be considered a surrogate clinical outcome or marker for clinical trials of amyloid-lowering treatments. Specifically, for trials of amyloid-targeti
COMMENT In this article, Aisen et al. argue that if new amyloid lowering immunotherapies (ALIs) were to come before the FDA with “clear-cut biomarker evidence” of amyloid lowering and acceptable safety profiles, approval should be granted prior to availability of
COMMENT This position paper proposes an interesting extension to evaluating outcomes of anti-amyloid immunotherapy: approving a drug based on safety and strong efficacy in amyloid clearance, and not requiring clinical outcome measures. Evidence for the amyloid hy
COMMENT Aisen et al. propose that regulatory agencies should consider conditional regulatory approval for amyloid-lowering immunotherapies based on evidence of amyloid removal combined with clear-cut fluid biomarker evidence. Safety would be taken into account as
COMMENT This report contributes substantively to an understanding of potential roles of astrocytes in Alzheimer’s disease and, in doing so, provides a stronger foundation for exploration of the astrocyte as a therapeutic target. Technically, it illustrates how fa
COMMENT This is a very interesting and thorough study investigating astrocyte heterogeneity in Alzheimer’s disease. Astrocytes are highly diverse in the brain, with several transcriptional and morphological subtypes. Serrano-Pozo and colleagues elegantly profile
COMMENT Aisen et al. suggest the possibility of treating individuals with biomarker evidence of amyloid plaques with anti-amyloid treatments, regardless of whether these individuals have cognitive impairment, and they provide a strong scientific rationale for thi
COMMENT I strongly endorse the arguments put forward by Aisen and colleagues for regulatory approval of Aβ-targeting therapies based on imaging and biofluid biomarker evidence, exactly as happened for the approval in 1984 of lovastatin, based on its cholesterol-l
