In mouse models of tauopathy, microglia populations are far from binary. Different activation stages emerge at different phases of disease, some marked by viral defense pathways.
New drug application is first for Alzheimer’s disease in the U.S. since 2003, and first based on amyloid hypothesis.
New synaptic profiling and imaging techniques are enabling scientists to zero in on synaptic proteins, including phospho-tau, that make the difference between clinical Alzheimer’s and resilience.
By pinpointing where tau pathology starts in a person’s brain, researchers better predicted future spread and determined small changes in tangle load.
Phospholipase C-γ2 acts downstream of TREM2 to rev up beneficial inflammation, phagocytosis, and cell survival.
In mice lacking the recycling protein GGA3, BACE1 trafficking stalls, local Aβ production increases, and axons swell. Does this explain the neuritic dystrophies seen in early AD?
Two cohorts—IDEAS and WHIMS—show Aβ accumulation and brain shrinkage in cognitively normal and impaired elderly who were exposed to levels of air pollution even within current EPA limits.
While the FDA weighs aducanumab’s marketing license application, Alzheimer’s researchers agree that the agency’s own statistician correctly assessed the data as weak. Most prefer that one more trial be done.
The modeling approach reinforces the idea that tau pathology propagates through the brain’s physical architecture, including neuronal networks.
In mice, forebrain neurons with hobbled retromers ooze fragments of tau and several BACE1 substrates into the CSF. Similar proteins are up in CSF from people with MCI and Alzheimer’s disease.
Could this forestall the amyloid cascade and the onset of Alzheimer’s disease?
Researchers found that bits of tau from the protein’s microtubule-binding region can be detected in the cerebrospinal fluid. These, not phospho-tau or total tau, reflect neurofibrillary tangles in the Alzheimer’s brain.
Breaking familiar gene-disease patterns, HTT trinucleotide expansions lead to huntingtin aggregates in prefrontal cortex. Noncoding caveolin 1 variants suppress its expression.
This astrocytic glycoprotein greases glial phagocytosis and reduces plaque burden in mice. The circadian clock protein Bmal1 suppresses it.
The enzyme degrades anti-inflammatory fatty acids in the brain. Blocking it with a brain-penetrant small molecule calmed A1 astrocytes, synapse-eating microglia, and improved amyloidosis and cognition in a mouse model.