8401 RESULTS
COMMENT This work provides an additional mouse model and research tool for the C9 ALS/FTD community. Because C9 ALS/FTD disease is a complex disease, with the expression of two mutant transcripts (sense and antisense) and six dipeptide repeat-containing proteins, ...
COMMENT This is a very nice addition to the building literature on mechanisms of toxicity from DPR expression in animal models. It brings to light a surprisingly specific mechanism, whereby poly(GR) alters mitochondrial ATP5A1, further linking mitochondrial ...
COMMENT This paper describes an interesting new poly(GR)-expressing mouse model. We will need a range of different models to ultimately understand the role of each DPR and their contribution to C9ORF72-repeat pathology, so this is a welcome addition. The most ...
COMMENT This paper nicely shows that expression of a poly(GR) in all the layers of the cortex under the control of a CamKII promotor can induce an ALS/FTD-related phenotype. A major advantage of this study is that the poly(GR) is expressed at a relatively low ...
COMMENT There is now substantial clinical data indicating that inhibition of Aβ generation via γ- or β-secretase inhibition is not effective and, at least in some cases, is associated with cognitive impairment. Over the last years, we have been good at defining ...
COMMENT The clinical failures of drugs to treat AD may be explained by the formation of cytotoxic Aβ oligomers and their pleomorphism. Indeed, many monoclonal antibodies (mAb) have been directed against monomeric Aβ, while ignoring until recently the toxic ...
COMMENT Dr. Hafner is correct in stating that analyzing the nuclear transcriptome "will miss information about the subcellular distribution of transcripts and local regulation of translation." I spearheaded a study of the synaptic transcriptome in MCI ...
COMMENT Our group has published on the impact of near-infrared pulsed-light stimulation in dementia, showing improved cognitive and behavioral functioning after 28 consecutive five-minute treatments. We are using this now in our clinical work, and are combining ...
COMMENT This is a tour de force by the teams of Li-Huei Tsai and Manolis Kellis. A particular strength is the separate treatment of early and advanced pathology, with analyses of early versus control, and late versus early. This helps distinguish changes in an ...
COMMENT Axonal protein synthesis is a mechanism to alter the local proteome in a spatially and temporally restricted manner. Many studies have demonstrated its importance in virtually every aspect of axonal biology, e.g., developmental growth, regeneration, ...
COMMENT My colleagues and I are encouraged by attention directed at modifiers of innate immune activity for treatment of AD. However, we urge caution in the application of anti-immune (including anti-TREM2) treatments in humans. The proposed Phase 1 work should ...
COMMENT The absolute improvement and placebo-relative improvements [in this study] are quite dramatic, and hopefully reflect physiologically healthy sleep. It's nice to see that there is robust efficacy in patients with Alzheimer’s disease, as the ...
COMMENT Both these studies are very interesting and will propel the field forward in enabling us to better model the human disease. For quite some time we’ve had a plethora of studies in model systems indicating aberrant lipid interaction of α-Syn as a clear mode ...
COMMENT Our understanding of Lewy pathology has not changed much since 1912, when Fritz Heinrich Lewy first reported the typical types of accumulations in the brains of patients. Since 1997–98, we have focused primarily on the fact that α-synuclein appears to be ...
COMMENT This study contributes important data on longitudinal tau PET changes across a large sample of individuals spanning the AD continuum from preclinical to dementia. The data provide additional support for a strong, longitudinal relationship between tau and ...
