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.
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API Colombian Trial of Crenezumab Missed Primary Endpoints
Topline results showed no statistically significant slowing of decline on either of two primary endpoints. Trends across multiple endpoints favored crenezumab.
TAURIEL Phase 2 Data Published
In people with mild AD, Genentech’s anti-tau antibody, semorinemab, did not slow cognitive decline.
Sans Microglia, Mice Develop CAA and Die Young
5xFAD mice lacking microglia develop cerebral amyloid angiopathy and amass calcium deposits. Most die by 6 months old.
LATEr Than You Think: TDP-43 Pathology Lurks in 40 Percent of Old Brains
Limbic-predominant age-related TDP-43 encephalopathy (LATE) most often co-occurred with AD pathology, but was detected on its own as well.
New Role for α-Synuclein: Stabilizing mRNA in P-Bodies
α-Synuclein prevents de-capping of transcripts, hindering their turnover. In human brain, α-synuclein accumulation correlated with slower mRNA decay.
Aggregates of TDP-43 in Muscle—Potential ALS Marker?
TDP-43 inclusions in intramuscular nerve bundles, paired with clinical criteria, may enable diagnoses at early stages of ALS.
Two ApoE Mutations Decrease Risk for Alzheimer's Disease
A case-control study of half a million people nabbed the variants. Both are rare, lie in the C-terminal lipid-binding domain, and one neutralizes ApoE4.
LRRK2 Inhibitor Hits Target, Appears Safe for Parkinson’s
In two Phase 1 trials, DNL201 reduced LRRK2 kinase activity in blood mononuclear cells. The inhibitor reached the same level in CSF as in blood. There were no serious side effects.
Behold PANTHOS, a Toxic Wreath of Perinuclear Aβ That Kills Neurons
Months before mice develop plaques, faulty lysosomes swollen with Aβ commandeer plasma, ER, and Golgi membranes, creating toxic rosettes around the nucleus. The neurons eventually burst, leaving behind plaques.
CRISPR Prevents Pathology in Cell and Mouse Models of ALS/FTD
Adeno-associated viruses carrying Cas9 and guide RNAs cut hexanucleotide repeats out of the C9ORF gene. RNA inclusions and poly-dipeptides became sparse.
In Progressive Supranuclear Palsy, Filamin-A Goads Tau Aggregation
The actin-binding protein associated with tau aggregates in people with PSP, and rare variants in the gene associated with the disease.
Does TSPO PET Measure Microglia Activation or Density?
A provocative new study suggests that unlike in mice, TSPO in people does not rise with microglial activation; instead, a higher PET signal reflects more microglia.
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.
FDA Approves Fujirebio’s CSF Test for AD—Quest Diagnostic Offers Plasma Test
The first FDA approval of a CSF test, and increased options for plasma testing, will give patients easier access to these diagnostic aids. Will physicians interpret them properly?
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