News and Events | Page 8 | Helen & Robert Appel Alzheimer’s Disease Research Institute

Lysosomal exocytosis releases pathogenic α-synuclein species from neurons in synucleinopathy models

Congratulations to the Sharma lab for their recent work on alpha-synuclein pathogenesis recently published in Nature Communications!

In collaboration with the Burré lab, also at the Appel Institute, the team led by Dr. Manu Sharma found that pathogenic alpha-synuclein species accumulate within neuronal lysosomes and are released through SNARE-dependent lysosomal exocytosis, providing a novel mechanism by which pathogenic alpha-synuclein transmit from neuron-to-neuron and spread...

A CRISPRi/a platform in human iPSC-derived microglia uncovers regulators of disease states

A collaborative effort between the Gan lab at the Appel Institute and the Kampmann lab at UCSF reveals regulators of disease states in a recent publication out now in Nature Neuroscience. The authors devised a fast and efficient method to generate induced microglia from iPSCs and developed CRISPRi/a platforms that can systematically discover regulators of microglia states and allow researchers to determine their function and therapeutic value. See the press release from WCM Newsroom...

Synaptic vesicle binding highlights interactions between synucleins are important to brain health

A collaboration between the Burré and Sharma labs, “Synaptic vesicle binding of α-synuclein is modulated by β- and γ-synucleins,” has recently been published in Cell Reports. Their work furthers our understanding of the composition of synuclein heteromultimers on the synaptic vesicle surface and shows that these synuclein heteromultimers govern the amount of physiologically active α-synuclein on synaptic vesicles. These findings highlight the need for a balance of synucleins for...

Mapping Dementia-Linked Protein Interactions Yields Potential New Treatment Targets

We’re excited to share our latest research out in CellPress NOW! Using APEX and AP-MS proteomics, we mapped Tau interactomes that were modified by neuronal activity and FTD mutations in hiPSC-derived neurons. Read the press release here. The full article is open access and can be read...

Targeting the Brain’s Immune Cells May Help Prevent or Treat Alzheimer’s Disease

Our recent study in Science Translational Medicine identifies a TREM2 R47H-specific microglial subpopulation in human AD brain and tauopathy mice, reminiscent of DAM and AKT hyperactivation which can be rescued by pharmacological AKT inhibition. Read the full article here.