Sjors Scheres, Michel Goedert on That Mystery “Density” in α-Syn Fibrils: Polyphosphate, Anyone?

COMMENT remains a mystery. Authors:  scheres_235491 mg Follow comments on this article:  0 References:  Molecular

Markus Damme on Divergent and Convergent TMEM106B Pathology in Murine Models of Neurodegeneration and Human Disease

COMMENT immunoblotting. The study also underscores the need for fibril-specific TMEM106B antibodies. Follow comments on

Nikolaos K. Robakis on Hypercholesterolemia and Alzheimer's Disease: Unraveling the Connection and Assessing the Efficacy of Lipid-Lowering Therapies.

COMMENT open new avenues for therapeutic exploration. Follow comments on this article:  0 Authors: 

Robert Vassar on Remembering Bruce Albala, 70, Leader in BACE Inhibitor Development

COMMENT Bruce had a brilliant career in both academia and industry and left an indelible mark on the Alzheimer’s disease drug development landscape. He led drug development efforts in several companies, most notably at Eisai, where he directed their BACE inhibito

Michelle Gee, Luigi Giorgi on Remembering Bruce Albala, 70, Leader in BACE Inhibitor Development

COMMENT It was with shock and incredible sadness that colleagues at Eisai received the news that Bruce Albala had passed away. Bruce was a senior member of the neurology clinical development department at Eisai from 2010 to 2019, where he led the development of e

Stefan Lichtenthaler on Remembering Bruce Albala, 70, Leader in BACE Inhibitor Development

COMMENT I am saddened by the sudden and much too early death of Bruce Albala. Bruce was an excellent scientist, a great colleague, a good friend, and a leading scientist in the development of BACE inhibitors for Alzheimer’s disease. Working with Eisai, Bruce was

Bahareh Ajami on Amyloid Plaques Turn More Toxic as They Age

COMMENT This study advances our understanding of amyloid plaque formation and maturation in AD by building on previous isotope labeling and mass spectrometry imaging techniques, while also introducing several key innovations. It utilizes the AppNL-F mouse model,

Douglas Galasko on Amyloid Plaques Turn More Toxic as They Age

COMMENT This study elegantly places a timetable on plaque formation in a transgenic mouse model (AppNL-F) selected to develop amyloid pathology relatively slowly, using stable isotope labeling, mass spectrometry, advanced microscopy and spatial transcriptomic ana

Melissa Murray, Baayla D.C. Boon on Amyloid Plaques Turn More Toxic as They Age

COMMENT This study investigates Aβ plaque pathology through a new mass spectrometry imaging method combined with isotope labeling (iSILK) in an Aβ knock-in mouse model (AppNL-F), and couples the plaque age with spatial transcriptomics. This approach enables the s

Santiago Sole-Domenech on A Match Made in Microglia? ApoE and Aβ Click in Lysosomes, Seeding Plaque

COMMENT Kaji et al. propose that fibrillar ApoE—likely forming in microglia lysosomes after internalization and delipidation of the lipid carriers—promotes aggregation of Aβ. The authors preaggregated HFIP Aβ by incubating a solution in PBS for 48 hours at 37°C,

Hui Zheng on A Match Made in Microglia? ApoE and Aβ Click in Lysosomes, Seeding Plaque

COMMENT The current work is built on the creation of a knock-in mouse model expressing a HaloTag-tagged APOE, thus allowing its in situ visualization and biochemical purification. Using this elegant system, coupled with various imaging modality and biochemical me

Jessica Young on A Match Made in Microglia? ApoE and Aβ Click in Lysosomes, Seeding Plaque

COMMENT Genetics studies point to endo-lysosomal, immune, and lipid pathways as dysfunctional in AD, and many of these genes are highly expressed in glia. In this study, Kaji et al., perform an impressive amount of experiments to show microglial cells are necessa

Jason Ulrich on A Match Made in Microglia? ApoE and Aβ Click in Lysosomes, Seeding Plaque

COMMENT This is a fantastic study from the Simons lab that brings together a lot of key observations into an attractive theoretical framework for how APOE and microglia conspire to form nascent amyloid fibrils to seed pathology. It begs the question of whether de

Greg Lemke on A Match Made in Microglia? ApoE and Aβ Click in Lysosomes, Seeding Plaque

COMMENT Kaji and colleagues use a variety of experimental approaches to demonstrate that, in the AD brain, lipid-associated ApoE is phagocytically internalized into microglia together with lower-order polymers of Aβ, and that ApoE facilitates the dense fibrillar

Per Hammarstrom on Amyloid Plaques Turn More Toxic as They Age

COMMENT This pioneering study by Hanrieder and co-workers aims to understand the initiation and progression of Aβ aggregate accumulation and correlations with CNS cell responses by spatial transcriptomics in the proximity of early and late Aβ aggregates. Chemical