Over the Span of AD, Roles of Astrocytes and Microglia Change
Reactive astrocytes spell trouble for synapses, while microglial transform from protective to destructive as disease progresses.
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Could Sumoylation Take Down Tangles?
The addition of SUMO2 to tau prevents its phosphorylation and aggregation, preserving synapses and memory in tauopathy mouse models.
Easing Microglial Brakes Alleviates Amyloid Pathology in Mice
An antibody against the inhibitory receptor LILRB4 prevented its binding to ApoE. The upshot? Microglia engulfed more Aβ fibrils and plaque load fell.
p-Tau217 Immunotherapy Alleviates Tangle Pathology in Mice
Two antibodies—one against the phosphoprotein, the other to tau’s N-terminus—restored proteostasis in the brain.
Multiple Strategies Seek to Banish α-Synuclein Aggregates
At AD/PD, scientists presented small molecules that break up fibrils and antibodies that target pathogenic forms of α-synuclein or hinder spread in iPSCs and mice.
At ADPD, Scientists Dissect the Ins and Outs of Tau Propagation
New findings shed light on the intracellular processes that dictate tau seeding inside and between cells, and which forms are toxic to neurons.
Skin Deep: Punch Biopsies Detect Synucleinopathies
In a small sample set, phosphorylated α-synuclein was detected in the dermis of four such disorders.
Mouse Models and Markers for Cerebral Amyloid Angiopathy, ARIA
Researchers at AD/PD showcased progress in modeling these conditions, detecting CAA, and potentially mitigating microhemorrhages.
In AD, Effects of Some Genetic Variants Limited to Cell Subtypes
One variant promotes expression of TMEM106b in a subset of excitatory neurons, reducing their numbers. Another boosts ApoE4 in microglia.
CSF Hugs Arteries to Squeeze into the Brain
Cerebrospinal fluid rides the pulses of cerebral arteries to enter the brain and spread into cortical tissue. This supports the existence of a human glymphatic system.
Therapeutic Contenders Target Hard-to-Reach Pockets of Tau
O-GlcNAcase inhibitors and a vaccine head to Phase 2. New antibody strategies co-opt the proteasome to clear intracellular and extracellular tau in preclinical models.
TauRx Parses Subgroups to Make the Case for Methylene Blue Derivative, Again
Based on exploratory endpoints and post hoc analyses, TauRx claims HMTM benefits a subgroup of participants with MCI. Trialists are unconvinced.
TREM1 Muddles Myeloid Cell Metabolism and Memory in Old Mice
In peripheral macrophages and microglia, the receptor disrupts glucose metabolism. TREM1-deficient amyloidosis mice also had healthier neurons, better memories.
Reverse Electron Flow in Microglia Linked to Neuroinflammation
In a multiple sclerosis model, activated microglia reverse electron transport (RET) in their mitochondria, creating oxidative stress. Blocking RET eased pathology.
AD/PD™ 2024: Advances in Science & Therapy
Fast Plaque Clearance with Little ARIA? So Teases Trontinemab at AD/PD 2024 TauRx Parses Subgroups to Make the Case for Methylene Blue Derivative, Again Therapeutic Contenders Target Hard-to-Reach Pockets of Tau Mouse Models and Markers for Cerebral Amylo
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