Peter Lansbury on Nearly Two Years After FDA Approval, Relyvrio Bombs Phase 3 for ALS

COMMENT This is a huge story. There are many lessons to be learned here. lansburyp_333756 0

Andres Norambuena, George Bloom on More on Moribund Mitochondrial Respiration Prior to Plaques

COMMENT We are grateful for the comments that Alzforum readers made to our bioRxiv preprint. Brain

Robert Baloh on Neuroprotective Extracellular Matrix Seen in C9ORF72 ALS/FTD Models

COMMENT This represents another advance in C9ORF72 modeling, by placing expression of one of two different artificially engineered DPR proteins (GR or PR) under the control of the endogenous C9ORF72 promoter. Interestingly, the authors found that lower motor neur

Takaomi Saido on More on Moribund Mitochondrial Respiration Prior to Plaques

COMMENT Norambuena and colleagues used an APP SAA / App NL-G-I knock-in mouse model of AD to demonstrate mitochondrial dysfunction in the very early stage of AD development. It is hard to understand why the authors used a copy model of our App NL-G-F and other kn

Russell Swerdlow on More on Moribund Mitochondrial Respiration Prior to Plaques

COMMENT I’d like to commend the authors on the technical sophistication of the work, for considering the possibility that mitochondria and energy-related metabolism are relevant to AD, and for offering a generally unique and innovative hypothesis. The authors rep

Angelika Harbauer on More on Moribund Mitochondrial Respiration Prior to Plaques

COMMENT Defects in proteostasis and the accumulation of toxic misfolded proteins, as well as mitochondrial dysfunction and a neuroenergetic crisis are intimately linked to each other in the pathogenesis of neurodegenerative diseases. This preprint tries to shed l

Guojun Bu on Different Cellular Mechanisms in Familial and Sporadic Alzheimer’s?

COMMENT The increased level of LRP1 in astrocytes observed in this study is quite interesting. It could be a contributing mechanism of protection by the APOE Christchurch variant. Other mechanisms could include reduced binding to HSPG and other apoE receptors suc

Marc Suárez-Calvet on Tau Fragments in Plasma Track with Tangles, Cognitive Decline

COMMENT The characterization of tau in CSF and blood has marked a milestone in the field of biomarkers for AD, and we now have a range of assays targeting different tau forms. However, most tau biomarkers are highly correlated among each other and this prompts th

Kanta Horie on Tau Fragments in Plasma Track with Tangles, Cognitive Decline

COMMENT As most phosphorylated-tau biomarkers available in blood or CSF reflect mainly Aβ-related pathology, there is an urgent need for the identification of cost-effective and scalable fluid biomarkers specific for tau aggregate pathology in Alzheimer’s disease

Tharick Pascoal on Tau Fragments in Plasma Track with Tangles, Cognitive Decline

COMMENT This study tests the performance of another blood test from the UGOT team in the well-characterized Biofinder cohort. The authors showed convincing results that support that the variance of their new NTA-tau assay is much better explained by tau PET than

Jeffrey Dage on Tau Fragments in Plasma Track with Tangles, Cognitive Decline

COMMENT Lantero-Rodriguez and colleagues have conducted a comprehensive characterization of the NTA-tau assay, which employs anti-tau mAb (HT7) for capture and anti-tau (Tau12) for detection. This assay was developed and validated by the Clinical Neurochemistry L

Alberto Lleó on From St. Louis to Beijing: AD Biomarkers Change Similarly Before Symptoms

COMMENT This impressive study characterizes the longitudinal biomarker changes in sporadic AD. The pattern of changes in other forms of AD, such as autosomal-dominant AD (Bateman et al., 2012) or Down Syndrome AD (Fortea et al., 2020) have previously been reporte

Michael Weiner on From St. Louis to Beijing: AD Biomarkers Change Similarly Before Symptoms

COMMENT These two papers describing the timeline of the trajectory from amyloid positivity to symptom onset are extremely important, with very practical implications for clinical trials and patient care. What is so remarkable is how similar the results are in the

Debomoy Lahiri, Bryan Maloney on Epigenetic Shenanigans—In AD, Chromatin Opens Up in Blood Immune Cells

COMMENT comments already posted in Alzforum. We have long maintained that there is an important role for epigenetic

Chiara Cirelli on While a Fly Sleeps, Its Glia Burn Neuronal Lipids to Refresh the Brain

COMMENT This is a beautiful study with compelling results. That the authors discovered a role for glia in protecting neurons from wake-related oxidative stress is quite unexpected and eye-opening. The next step will be to test the extent to which this mechanism a