Without SORL1, Endosomes Swell in Neurons but not Microglia
Induced neurons lacking the Alzheimer’s risk gene can’t properly recycle APP.
NEWS
Shiny SEQUIN: New Technique Counts Synapses Over Large Brain Volumes
Using a form of confocal microscopy and automated software, the method allows researchers to rapidly identify functional synapses within brain structures.
Simulating Tangle Spread Along Axons, Scientists Predict Tau PET Patterns
The modeling approach reinforces the idea that tau pathology propagates through the brain’s physical architecture, including neuronal networks.
Molecular Transport Vehicle Shuttles Therapies into Brain
Built to cross the blood-brain barrier, the vehicle delivers therapeutic antibodies, enzymes, and potentially small molecules such as oligonucleotides.
Umbilical Cord With Presenilin Mutation Births New Cell Model of Familial AD
Umbilical cord stem cells from presenilin 1 E280A carriers, once differentiated into cholinergic-like neurons, pumped out Aβ42 and accumulated phosphorylated tau and apoptotic markers.
Paper Alert: CryoEM Structures of α-Synuclein Published
In stark contrast to Aβ and tau fibrils, α-synuclein fibrils are asymmetric, comprising two different protofibrils.
In Colombian Alzheimer’s Kindred, Blood NfL Climbs 22 Years Before Symptoms
The plasma biomarker neurofilament light was able to distinguish individual mutation carriers from noncarriers three years prior to onset.
Massive Proteomics Studies Peg Glial Metabolism, Myelination, to AD
Separately, cerebrovascular disease drove an uptick in neurofilament light in the brain, indicating neurodegeneration.
Virtual Exhibit Hall
Alzforum encourages users to visit the Virtual Exhibit Hall, where companies showcase their newest initiatives, products, and services. We welcome F. Hoffmann-La Roche, joining our other exhibitors — Biogen, BioLegend, Dash Genomics, Inc., Abcam, BrainXell, and the Jackson Laboratory.
SPOTLIGHT
Simulating Tangle Spread Along Axons, Scientists Predict Tau PET Patterns
How do tangles spread through the brain? New modeling reinforces the idea that spread occurs through the axonal connections between brain regions. Researchers simulated the advance of tangles from entorhinal cortex through a virtual brain using atlases of axonal and functional connectivity. When they compared the resulting patterns to actual tau PET scans, the axonal map best predicted tangle distribution. In regions with amyloid plaques, more tangles accumulated than the model predicted, reinforcing the idea that plaques promote tau pathology.
The Barrier Breach You Want to See
Scientists have engineered a specialized "vehicle" capable of whisking all manner of therapeutic molecules across the blood-brain barrier. It is an antibody fragment equipped with a domain that latches onto the transferrin receptor, which normally ushers transferrin into the brain. Using the vehicle, researchers delivered BACE1 antibodies, as well as an enzyme that is lacking in a lysosomal storage disorder, into the brains of mice and monkeys.
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