Death by Goo: TDP-43 Gels Paralyze Proteasomes in Neurons
Cryo-electron tomography reveals amorphous blobs of TDP-43 C-terminal fragments. They ensnare stalled proteasomes in the cytosol.
6471 RESULTS
Sort By:
Cryo-electron tomography reveals amorphous blobs of TDP-43 C-terminal fragments. They ensnare stalled proteasomes in the cytosol.
Atomic-level analysis of the protein’s C-terminal end suggests a floppy region key for the delicate process of forming functional oligomers. Mutate it slightly, and it becomes an aggregating machine.
Using a new optogenetic model for TDP-43 phase transitions, scientists see the protein aggregate outside, not inside stress granules. The model distinguishes physiological from abnormal phase transition.
VAMP2 helps distinguish pure dementia with Lewy bodies from DLB with Alzheimer’s. A synaptic protein panel distinguished FTLD-TDP-43 from FTLD-tau.
The blood protein tempers APOE4 risk in E2 carriers yet accentuates it in E4 homozygote people.
New, unbiased single-cell methods uncover coordinated changes in cell populations and their interactions. These correlate with disease pathology, progression.
In an amyloidosis mouse, inhibiting the endosomal proton leak channel NHE6 sped up recycling of ApoE. This slashed amyloid deposition and restored synaptic plasticity.
Cognitively normal older adults with high levels of the biomarker slid quickly toward dementia.
A few attempts at Alzheimer’s therapy claim hints of promise in early clinical trials, though several did not include placebo controls.
At LATE 2022, researchers hashed out neuropathological and clinical characteristics of limbic predominant age-related TDP-43 encephalopathy, a major contributor to late-life cognitive decline and potential bungler of AD clinical trials.
Different polymorphisms in MS4A genes up- or downregulate levels of TREM2, modulating levels of the shed ectodomain in the cerebrospinal fluid and AD risk.
Single-nuclei expression analysis identified different cell clusters from people who carried autosomal-dominant Alzheimer’s mutations or risk variants for late-onset AD. Also, microglia RNA-Seq goes big.
Shrinkage of distinct brain regions in the frontal and temporal lobes may unsuppress neural activity in the dorsal stream, a region involved in visual perception.
New research reveals fundamental roles for astrocytes and microglia in shaping neural circuits.
The U.S. Food and Drug Administration will convene an advisory committee to guide its decision, which will affect how widely available the treatment will be.