Adam Bachstetter on Do Rod-Shaped Microglia Dampen Hyperexcitability in ALS?

COMMENT biology: Translation and comments on Pío del Río-Hortega 1919 series of papers on microglia. An update on

Rene Frank on Organization of Aβ Plaques and Tau Tangles Illuminated in AD Brain

COMMENT Our published paper now also includes much-improved sub-tomogram averaging of in-tissue tau filaments, using Warp/M and Relion, developed by Dimitry Tegunov at Genentech and Sjors Scheres at the Medical Research Council Laboratory for Molecular Biology, r

Rahul Nagvekar, Justin You on C1q from Microglia Meddles in Neuronal Translation

COMMENT This exciting paper beautifully complements previous work showing the role of microglial C1q in synaptic pruning during neurodevelopment and neurodegeneration alike (Stevens et al., 2007; Hong et al., 2016; Wilton et al., 2023). This paper elegantly revea

Serena Carra on C1q from Microglia Meddles in Neuronal Translation

COMMENT In Alzheimer's disease, microglia are activated when they recognize the Aβ peptide, secreting a variety of inflammatory factors and neurotoxins, leading to neuronal damage/death. One of these factors, the complement C1q, is thought to modulate phagoc

Andrea Tenner on C1q from Microglia Meddles in Neuronal Translation

COMMENT Overall, this manuscript provides provocative novel observations and hypotheses that expand our knowledge of the potential roles of C1q, a recognition component of the innate immune system and of the classical complement pathway. C1q has been shown to be

Nicola Fattorelli, Renzo Mancuso on C1q from Microglia Meddles in Neuronal Translation

COMMENT This exciting and thought-provoking work by Scott-Hewitt et al. uncovers a new intraneuronal function for the microglial secreted protein C1q. The authors performed C1q co-immunoprecipitation from synaptosomes isolated from developing, young adult, and ad

Borislav Dejanovic on C1q from Microglia Meddles in Neuronal Translation

COMMENT The study unveils the fascinating and unexpected discovery that C1q regulates protein homeostasis in the aging brain independently of its role in the complement pathway. Our research, along with that of others, including Beth Stevens’ lab, has demonstrate

Kim Green on C1q from Microglia Meddles in Neuronal Translation

COMMENT This is an incredibly well-done and compelling study that convincingly demonstrates that a microglial-derived protein is taken up by neurons and modulates their function. We know that C1q has a diverse array of functions, particularly in the extracellular

Gabriela Constantin on Sex-dependent APOE4 neutrophil-microglia interactions drive cognitive impairment in Alzheimer's disease.

COMMENT Until about 10 years ago, neutrophils were considered a homogenous population of short lived, terminally differentiated cells with low transcriptional capacity that release a limited number of cytokines, suggesting highly conserved, specialized immune and

Jonathan Kipnis on Sex-dependent APOE4 neutrophil-microglia interactions drive cognitive impairment in Alzheimer's disease.

COMMENT The study by Rosenzweig et al. on the sex-dependent interactions between APOE4 neutrophils and microglia in Alzheimer's disease is very interesting and important. The authors have elegantly demonstrated the critical role of IL-17 signaling in cogniti

Costantino Iadecola on Sex-dependent APOE4 neutrophil-microglia interactions drive cognitive impairment in Alzheimer's disease.

COMMENT This study is of interest as it provides new insights into the sex dependence of the impact of ApoE4 on AD pathobiology. The inclusion of human data combined with experimental validation are major strengths of the paper. The identification of a new class

Michael Ward on A First for Proteinopathies—Heteromeric Fibrils

COMMENT These parallel discoveries by the Lee and Ryskeldi-Falcon teams are seminal. Together, they conclusively show that two distinct proteins, ANXA11 and TDP-43, co-assemble into organized heteromeric amyloid filaments in FTLD type C and in a subset of other T

Ian Mackenzie on A First for Proteinopathies—Heteromeric Fibrils

COMMENT I think this is a very interesting and exciting discovery for several reasons. The finding of a novel type of filament as a consistent feature of FTLD-TDP type C samples confirms that these cases represent a distinct entity, and validates the current path

Lary Walker on A First for Proteinopathies—Heteromeric Fibrils

COMMENT In the beginning, amyloid was identified by tell-tale morphologic and staining characteristics, and little was known about its constituent proteins. As analytic methods progressed, amyloids became increasingly defined by their principal polymeric proteins

Oleg Butovsky, Neta Rosenzweig on T Cells in the Brain Goad Microglia to Muddle Myelin

COMMENT will proceed directly to our comments.  In our previous work (Yin et al., 2023), we identified