New study in Nat Neurosci finds TGFβ signaling is crucial for maintaining microglial resilience to myelin degeneration in the dorsal column of the spinal cord during aging & emergence of TGFβ signaling-sensitive microglial & disease-associated oligodendrocyte subsets www.nature.com/articles/s41...

Excited to share our new study identifying soluble DLK1 as a novel microglia-derived senescence factor. sDLK1 induced hypomyelination, oligodendrocyte dysfunction, & altered neuronal activity in iPSC-derived neurons @gladstoneinst.bsky.social www.biorxiv.org/content/10.6...

Proud to announce our collaboration with @blurtonjoneslab.bsky.social & the Paz lab showing that transplanted human iPSC-derived microglia in a PGRN KO mouse model restores progranulin in microglia and rescues pathology, circuitry, and behavior. Preprint out now: www.biorxiv.org/cgi/content/...

🌲Season’s greetings from the Gan Lab!🌲 Warm wishes for a restful, connected, & rejuvenating turn of the year. For a glimpse into our lab life and research this year, check out: www.ganlab.org

AD genetic risk links microglial immunity and cholesterol. Our new BioRxiv study identifies CH25H-derived 25-HC as a toxic lipid downstream of cGAS–STING–IFN that drives tau spread, inflammation, and neurodegeneration, offering a tractable therapeutic pathway. www.biorxiv.org/cgi/content/...

Congratulations, Dr. Caitlin Castagnola! Last Friday, Dr. Castagnola defended her thesis on microglia-neuron interactions. Her humble manner, as always, belied the magnitude of work she’s accomplished in the Gan lab. We are so proud of her and excited for all her future chapters!🥳👩‍🔬🧪

Our new study in @molneurodegen.bsky.social shows that microglial DAP12 controls tau buildup and drives myelin loss by mediating a harmful tau-induced SLIT2 signal from neurons to oligodendrocytes link.springer.com/article/10.1...

New study in Neuron: ApoE2 and ApoE3 Christchurch-containing lipid particles protect neurons from ferroptosis by effluxing oxidized lipids through ABCA7. This rescues lysosomal defects, shields ApoE4 hippocampi from lipid toxicity, and restores neural activity www.cell.com/neuron/abstr...

New study from Jiang group gives clues to Down syndrome patients' resilience to AD: a DS-linked myeloid mutation (CSF2RB A455D) protects engrafted human microglia against tau by suppressing harmful IFN signaling, boosting phagocytosis, & reducing microglial senescence www.nature.com/articles/s41...

🍁Feeling grateful. Happy Thanksgiving from the Gan lab & Appel Institute!🍁

A study from the Sun lab reveals that biased CCKBR–Gq/Gi signaling regulates AD pathology & a synthesized CCKBR–Gq agonist (3r1) provides therapeutic benefits by upregulating ADAM10 & PLCB4. This work highlights CCKBR biased signaling as a promising drug target for AD www.cell.com/cell/fulltex...

New in Science!: Microglial FPR1 is a CNS-specific driver of demyelination. Deletion in MG or CNS macrophages protects against myelin loss, while peripheral deletion helps only partly. CNS-penetrant FPR1 antagonist (T0080) reduces ROS, inflammation & disease severity www.science.org/doi/10.1126/...

Thrilled to publish our new study on #mitochondrial ROS coming from complex III, revealing this key site in #astrocytes 🎯as a crucial immunometabolic signal transducer🤯 and potential therapeutic target for #dementia #FTD 💊 rdcu.be/eOc0m 👈💪 Great commentary by H. Pan and F. Yin🤩! tinyurl.com/4hdytw4c

Two separate studies from Gitler & Fratta labs reveal nuclear loss of TDP-43 disrupts RNA processing by altering alternative 3′ end cleavage & polyadenylation. They uncover new molecular signatures & shed new light on TDP-43 pathology www.nature.com/articles/s41... www.nature.com/articles/s41...

New article @natneuro.nature.com by @yaleneuro.bsky.social Suzhou Yang & @kavliatyale.bsky.social Postdoc Fellow @zhenlei.bsky.social, highlighting studies by @frattalab.bsky.social Gitler & La Spada labs on the role of TDP-43 on mRNA 3' end in ALS @yalerna.bsky.social www.nature.com/articles/s41...

Fascinating study from the Mao & Jiang lab: four amino acid residues unique to naked mole-rat cGAS, but absent in humans, are critical for efficient DNA repair, delaying aging and expanding life span. www.science.org/doi/epdf/10....

Mao, Han & Dawson labs reveal air pollutant PM2.5 triggers αSyn misfolding, forming a pathogenic strain (PM-PFF) that drives Lewy body dementia. This study illuminates the link between air pollution & neurodegenerative disease, offering insights for public health www.science.org/doi/10.1126/...

Collaborative work from Zhang, Cai & Peng labs identifies a glia-neuron protein co-expression subnetwork as a central driver of AD from multiscale genetic and proteomic analyses. AHNAK emerges as a key astrocytic driver whose downregulation reduces pTau & Aβ levels. www.cell.com/cell/fulltex...

Wu lab discovers early neuronal hyperactivity in TDP-43 induces rod-shaped microglia, which attenuates cortical hyperactivity, suggesting a neuroprotective role. Coincidentally, TREM2 signaling also promotes rod-shaped MG & neuroprotection. www.cell.com/immunity/abs...

New study from Yu & Sun identifies TFEB as a molecular link between neurons & oligodendrocytes (OL) in myelination. Neuronal signals trap TFEB in OL's cytoplasm, keeping TFEB from entering nucleus & repressing cholesterol biosynthesis genes, which causes hypomyelination www.cell.com/cell-reports...

Interesting study from Xu, Zhang & Mo labs: oxidized mtDNA can transform into Z-DNA & activate ZBP1–RIPK1–dependent inflammation in AD microglia. This highlights ZBP1–RIPK1 as a key regulatory axis of neuroinflammation & offers novel insights on AD inflammatory networks www.cell.com/immunity/ful...

🏆🏆🏆 CONGRATULATIONS to the winner of the PBL Assay Science Best Speaker Award Sarah Naguib @sarahnaguib.bsky.social Title: Elucidating the neuroprotective mechanisms of human microglial replacement therapy in FTD and PD Thank you PBL Assay Science for sponsoring the award

The Kolachama Lab is tackling the PET scan bottleneck in Alzheimer’s diagnosis with an AI model that predicts amyloid-β & tau status from 12,185 patients across 7 cohorts, offering a scalable alternative for pre-screening & guiding PET imaging. www.nature.com/articles/s41...

Exciting finding: Endogenous lithium is essential for brain health and its deficiency contributes to the onset and progression of Alzheimer’s disease, by activating GSK3β—leading to impaired Aβ clearance and synapse loss 🧠 Led by Dr. Bruce Yankner @harvardmed.bsky.social 🔗 doi.org/10.1038/s415...

By developing an antibody-based method using mass spec, this study uncovered >200 UFMylation sites across mouse tissues—including on myosin. Myosin UFMylation is elevated in skeletal muscle from people with ALS, suggesting in vivo UFMylation is more dynamic than expected www.cell.com/cell-reports...

Fascinating study from Hyman, Alberti & Mittal labs reveals how stress granules promote TDP-43 aggregation through intra-condensate demixing driven by Cys oxidation & hydrophobic patch contacts, marking the crucial role of stress granules & opening new doors for therapy. www.cell.com/cell/fulltex...

The Sirota & Huang labs identified a novel letrozole–irinotecan combination therapy that improves memory and reduces pathology in Alzheimer's disease models—showcasing a transformative drug discovery approach rooted in human transcriptomics and real-world clinical data www.cell.com/cell/fulltex...

New from Tilgner & Gan labs: Using ScISOr–ATAC, we found that splicing patterns differ across cell states within the same cell type in frozen primate cortex, and that oligodendrocytes in Alzheimer’s show high dysregulation in splicing & chromatin. Read more: www.nature.com/articles/s41...

🚨Our new paper is out!🚨 We uncover a protective mechanism of the rare APOE3 Christchurch (R136S) mutation against tauopathy—by suppressing microglial cGAS–STING–interferon (IFN) pathway, a key inflammatory axis triggered by tau. www.sciencedirect.com/science/arti...

Our 12th Annual Appel Symposium was a huge success! Record attendance, insightful faculty speakers, and a vibrant poster session sparked meaningful conversations and highlighted the innovative research at WCM. A sincere thank you to all who attended and the WCM teams who made this event possible.

Congratulations, Akida Abulimit @akidaabu.bsky.social, for winning 3rd place in Poster Presentation at the Weill Cornell Graduate Program in Physiology, Biophysics and Systems Biology 2024 Retreat!

Our lab enjoyed the exciting scientific advancements & fruitful discussions at the NYAS Therapeutic Approaches to Protein Misfolding in Neurodegenerative Disease conference this week! Dr. Gan presented on enhancing resilience against tau alongside other stellar speakers. www.nyas.org/shaping-scie...

Exciting work @blurtonjoneslab.bsky.social: CRISPR-engineered iPSC-microglia use the plaque-responsive CD9 promoter to deliver Aβ-degrading neprilysin across the brain-- reducing plaques, inflammation & synaptic loss. A promising new cell therapy platform for AD www.sciencedirect.com/science/arti...

According to researchers Kanta Horie, Gemma Salvadó, Rama Koppisetti, Oskar Hansson, Randall Bateman, et al. newly developed blood test for #Alzheimers not only aids in diagnosis of Alzheimer's but also indicates how far it has progressed. Learn More in Nature Medicine www.nature.com/articles/s41...

Fascinating study from Nature reveals crosstalk between mitochondrial translation, ROS activity, and the membrane retromer complex. www.nature.com/articles/s41...

A CSF proteomics study in Nature Medicine of 3,397 individuals identified synaptic proteins YWHAG:NPTX2 as key correlates of cognitive impairment in AD, highlighting synapse dysfunction as a core driver of AD dementia. #Alzheimers #Proteomics #Neurodegeneration www.nature.com/articles/s41...

Big congratulations to Dr. Celeste Parra Bravo! 🎓 Last Tues, 3/25, Dr. Parra Bravo defended her thesis with command and grace. Next, she’s headed to a postdoc in the Rosato lab at Dartmouth. We’re so proud of all she’s accomplished and can’t wait to see her continued contributions to science!🧪🔬🧠