“Frustrated Oligomers” Slow Aggregation of Aβ42
Heterogenous oligomers that include shorter Aβ peptides, such as Aβ37 and Aβ38, along with Aβ42 do not form fibrils, slowing plaque growth.
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Single-Cell Sleuthing Nabs Neurons Prone to Perish in Parkinson’s
A population of AGTR1-expressing dopaminergic neurons in the ventral slice of the human substantia nigra were selectively vulnerable in Parkinson's disease. These cells also expressed the most PD risk genes.
Membrane Border Patrol: Cholesterol Stymies Tau Uptake, Aggregation
Depleted of cholesterol, neurons laid out the welcome mat for tau aggregates, which readily crossed into the cytosol and seeded aggregation there. Adding cholesterol blocked entry and seeding.
With Age, Slower Protein Turnover May Predispose to Neurodegeneration
Proteins stuck around longer in the oldest mice. Those involved in neurodegeneration had the most extended lifespans.
Reactive Astrocytes Boot Basic, Dysfunctional Lysosomes
When provoked by cytokines, astrocytes change their gene expression so as to make their lysosomes overly alkaline, rendering them dysfunctional. Astrocytes then dump lysosomes' contents outside, creating a neurotoxic culture medium.
TMEM175 Maintains Lysosome pH by Pushing Out Protons
While TMEM175 ushers potassium ions out of neutral lysosomes, it shuttles protons out of acidic ones. Sans TMEM175, lysosomes become too “tart,” and stop working. Two papers say so.
How Does a Neuron Avoid Aggregation of Liquid Protein Droplets?
Mutations spur fibrillization, while methylation and autophagy keep droplets nice and fluid.
Too Clingy: Extra Hydrogen Bond Prompts Protein Aggregation
Certain mutations in TDP-43, tau, and NfL add one hydrogen bond to their low-complexity domains. This warps phase transition and strengthens self-aggregation.
In Down's Syndrome, Blood P-Tau217 Detects Plaques and Tangles
In young adults with Down’s, plasma phospho-tau217 correlated with amyloid and tau PET positivity. With great accuracy.
Scientists Discover a Common Distress Signal in the Blood-Brain Barrier
The same endothelial cell response is found in various models of brain disease.
Potent TREM2 Antibody Stirs Microglia to Prune Plaques in Mice
A tetravalent IgG1 prompts TREM2 to cluster, boosting the receptor’s activation 100-fold. Treated mice had fewer plaques, better memories.
LRRK2 Variants Keep α-Synuclein from Forming Tetramers
The Parkinson’s-related proteins promoted pathological hyperphosphorylation of α-synuclein.
Blood Metabolome Predicts 23 Diseases, Including Dementia
Analysis of 168 metabolites in one blood sample foretold 10-year risk of developing common disorders.
Forced Into Fat-Burning Mode, Microglia Gobble Up Plaques, Protect Neurons
Blocking glycolysis triggers microglia to crank up lipid metabolism, boosting ATP production and improving phagocytosis. In Alzheimer’s disease, the opposite happens.
In TRAILBLAZER, Plasma GFAP Falls, but NfL Continues to Rise
While GFAP seems a sensitive biomarker of Aβ plaque removal, NfL might respond more slowly.
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