11522 RESULTS
COMMENT It is exciting to see the first paper investigating longitudinal locus coeruleus (LC) integrity and longitudinal tau-PET in vivo! Bueichekú and colleagues expanded on their previous pioneering studies. In a cohort of almost all cognitively unimpaired olde
COMMENT The is another in a series of articles discussing the integrity of locus coeruleus norepinephrine projection neurons and cortical tau pathology and cognition in Alzheimer’s disease. The authors examined whether LC changes precede tau deposition in the med
COMMENT The noradrenergic locus coeruleus (LC) is among the first regions in the brain to accumulate hyperphosphorylated tau pathology, prior to the medial temporal lobe (MTL) and the cortex, in the prodromal stages of Alzheimer’s disease (AD). Because the LC pro
COMMENT This paper is very important for the field in several aspects. It builds logically from the beautiful work that Heidi Jacobs has been doing on the importance of the neuromodulatory subcortical system, with a special focus in the locus coeruleus in AD prog
COMMENT Bueichekú and colleagues conducted a study using multiple imaging biomarkers, including a 3T MRI sequence dedicated to locus coeruleus (LC) quantification, as well as amyloid and tau PET. They showed that LC integrity predicted longitudinal tau PET accumu
COMMENT Cooper et al. report interesting findings consistent with the notion that SORL1 may operate as an intracellular receptor for internalized tau, in a process that modulates tau seeding and may thus be relevant for tau spreading in AD. While there is mountin
COMMENT In this study by Wagemann et. al, gantenerumab and solanezumab have been studied in the context of dominantly inherited Alzheimer disease (DIAD), and they have shown different effects on downstream biomarkers. Previously reported results (Salloway et al.,
COMMENT This is an interesting mechanistic study by Cooper et al., looking at the interactions between tau and SORL1, a protein with known associations to AD. This new study expands on the authors’ prior biochemical work looking at the tau-LRP1 interaction and it
COMMENT SORL1 is best known as a modulator of APP sorting, metabolism, and amyloidogenesis. This new data extends the action of SORL1 to tauopathy, providing an unexpected convergence of two key pathways in Alzheimer pathogenesis. Tau aggregates form in neurons a
COMMENT The take-home message for me is that any assertion of a single protein “receptor” for tau at the surface should be taken with a grain of salt. This paper purports to show that SORL1 is a “receptor” for tau. However, one of the final figures indicates that
COMMENT The paper is interesting and potentially important. That retromer-regulated trafficking is important in tauopathies, including Alzheimer’s disease, is well-established (e.g., Mishra et al., 2023). However, the direct binding of tau to SORL1 is a new findi
COMMENT This paper by J.M. Cooper et al. is a well-executed study that advances our thinking about the route tau travels once internalized. In essence, the problem we face is that, internalized via LRP1 through which it enters endosomes, tau must escape the endos
COMMENT This is a very nice study from the DIAN-TU team, reporting the effects of anti-amyloid therapy with gantenerumab and solanezumab on CSF and plasma biomarkers as measured by the Roche NeuroToolKit in dominantly inherited Alzheimer’s disease. Although the s
COMMENT I agree w Dr. Young that this is an elegant study, and with other colleagues' qualifiers related to limitations of this thought-provoking new insight. However, I would like to stress one issue that might bear wider relevance: Endolysosomal toxicity b
COMMENT I’m excited about these findings, which bolster the growing body of work that neurons transfer lipids to glia, most likely to alleviate their own oxidative damage, and that lipids accumulate in Alzheimer’s brains. The role for AMPK described here is intri
