11505 RESULTS
COMMENT I want to start by congratulating the EMA CHMP for their courageous and forward-thinking decision to revise the verdict on the approval recommendation for Leqembi. This marks a critical step in addressing the immense challenge posed by Alzheimer’s disease
COMMENT The manuscript by Alberto Serrano-Pozo and colleagues elegantly describes the dynamic changes in astrocytes across various brain areas, and at different stages of Alzheimer’s disease. This study is extremely important as it highlights the dynamics of astr
COMMENT As commented above by colleagues, that is the crucial missing piece to better inform this and future
COMMENT While Aisen et al. argue for regulatory approval of amyloid-lowering therapies based on biomarker evidence, we currently caution against prioritizing biomarker outcomes over robust clinical endpoints in Alzheimer’s disease therapeutic trials for the follo
COMMENT This is an impressive study by Serrano-Pozo, Hyman, Das and colleagues that explores astrocyte transcriptomic molecular programs in aging and Alzheimer’s Disease. Using single-nucleus RNA sequencing of more than 600,000 astrocytes from five brain regions,
COMMENT Many neurodegenerative disease-associated risk factors, including ApoE, exert key functions in endo-lysosomal and lipid homeostasis. ApoE is central to the pathology of Alzheimer´s disease since heterozygous, and even more so homozygous, ApoE4 carriers ha
COMMENT With the expansion of the number of APOE variants that affect the risk of AD, there is a great opportunity to define functional effects of the ApoE proteins that track with risk. Guo et al. took on a Herculean task of testing many aspects of neuronal lipi
COMMENT In this paper, Guo and colleagues offer important mechanistic insights into the role of AD-associated ApoE variants in lipid transfer and intracellular accumulation. This is achieved using a reductionist approach, expressing various disease-associated Apo
COMMENT The authors propose an inverse relationship between lipidated ApoE-LDLR interactions and the risk of late-onset Alzheimer’s disease. This model is supported by observations that increased binding between lipidated ApoE and LDLR results in lysosomal impair
COMMENT This comprehensive study highlights protective roles of APOE2 and APOECh alleles in altered LDLR recycling and reduced lipofuscinosis, a lysosomal pathology induced with age and neurodegeneration. Briefly, these protective alleles lead to reduced endosoma
COMMENT This is a very interesting paper exploring the protective mechanism of APOE2 in AD using mostly in vitro cell-based assays. Research on the biology and pathobiology of ApoE, the strongest genetic risk factor for AD, has become increasingly interesting, an
COMMENT This very exciting story from Guo, Di Paolo, and collaborators brings ApoE-receptor binding back into the limelight of Alzheimer’s disease research. In a convincing manner, the team shows how ApoE2 and ApoE Christchurch have reduced LDLR binding, thereby
COMMENT First off, this is a very important paper and, in my view, constitutes a real advance in our understanding of how the ApoE alleles/isoforms so profoundly alter one’s risk for developing Alzheimer’s disease. The data suggest that this lies in the different
COMMENT The IWG highlights the crucial distinction between three categories: 1) asymptomatic at-risk individuals, who have an increased yet still low probability of developing AD; 2) presymptomatic individuals, who are at a very high risk of developing the diseas
COMMENT The conclusion that the Biondi bodies may contribute to the reduction in CSF production in aging, and possibly in age related neurodegenerative disease in which CSF clearance may be reduced, is certainly of interest. Another aspect that could be of intere
