8551 RESULTS
COMMENT I agree with Paul Aisen’s remarks. The evidence that Aβ is a key initiator of AD is overwhelming, and BACE inhibition early in the disease process should therefore prevent AD. However, BACE has many substrates that perform important functions in the brain ...
COMMENT This is one more terribly disappointing result in our field. BACE inhibition would seem to be a powerful tool against the accumulation of toxic amyloid species that drives AD neurobiology in the early stages of the diseases. Secretase inhibition has been ...
COMMENT The noradrenergic locus coeruleus (LC) in the brainstem shows functional and structural decline in a number of the most frequent neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and Lewy Body dementia (Jacobs et al., 2019; ...
COMMENT The work of Dahl and colleagues confirms the supposition that the locus coeruleus may be spatially organized in rostral and caudal segments, each projecting to particular target regions that exert various neurobehavioral functions, among them being memory ...
COMMENT Konttinen and coworkers add to the rapidly growing body of work examining the effect of AD risk factors using induced human microglia derived from iPSCs. The observed reductions in phagocytosis and increased inflammatory cytokine production in APOE4 ...
COMMENT Konttinen et al. have developed another microglia protocol based on human iPSC-derived primitive (but not definitive) erythromyeloid progenitors induced by hypoxia. The protocol is similar to but slightly simpler than that described by Abud and colleagues ...
COMMENT Our group and others have shown that postmortem variables such as locus coeruleus neuron number, density, and volume are all associated with antemortem performance in multiple cognitive domains, including memory. If you think about the role of forebrain ...
COMMENT This is a very creative methods-development paper that will likely fill a much-needed niche in the mitochondrial research field. Over the past few decades it has increasingly become clear that mitochondria are not equivalent between cell types. For ...
COMMENT The work from Fecher et al. is a very innovative solution to the older problem of estimating if mitochondria in major cell types of the mammalian brain are different. Based on their differing physiology and energetic requirements, it is gratifying, if ...
COMMENT In this very nice study, Misgeld’s group has engineered a set of MitoTag mice expressing GFP in the outer mitochondrial membrane (OMM) in a cell-type-specific manner. Importantly, they demonstrate that GFP-OMM-tagged mitochondria can be purified in ...
COMMENT This study has many strengths, including the focus on long-term survivors of “civilian” TBI, a very common public health problem, and the deep phenotyping of individuals with multiple cognitive measures, MRI sequences, and genetic and fluid-based ...
COMMENT These papers by Siahaan et al. and Tan et al. add to a growing body of work emphasizing the importance of phase separation in biology, and the specific importance of this work in tau biology. Previous work by the Hyman laboratory demonstrated the ...
COMMENT Phase states of tau can regulate microtubule function These new tau papers advance our knowledge of tau protein function at a mechanistic level. Previous work showed that tau is an RNA-binding protein capable of undergoing liquid-liquid phase separation ...
COMMENT Both studies elegantly identify novel interactions between tau and microtubules (MTs) in a physiological setting, either in regulating tau condensation or in protecting MTs from depolymerizing. I have been reminded of a paper from the Safinya lab on the ...
COMMENT This latest work from Kim Green’s laboratory shows that prolonged microglia depletion in 5xFAD mice (a common mouse model for AD) greatly reduces plaque formation, thus confirming recent findings by another group (Sosna et al., 2018). Notably, this ...
