A new mass spectrometry analysis provides the most thorough catalog yet of modifications to tau.
Findings suggest a severe blow to the head twists the protein's backbone, which may lead to neurofibrillary tangles.
Clever optical corrections reveal microglia and neurons through the intact mouse cranium.
A C-terminal fragment of APP recruits the protein APPL1 to endosomes, causing the enlarged, overactive vesicles seen early in Alzheimer’s disease.
The foundation recognizes the two researchers for their work on the molecular underpinnings Alzheimer’s disease.
Soluble APPα ramps up early in a mouse model of Fragile X Syndrome, and may promote symptoms of the disease. Blocking the peptide’s production could be a treatment strategy.
In some people, proteins in the cerebrospinal fluid trend toward an Alzheimer’s-like profile as early as age 45.
Mutant SOD1 prevents immature lysosomes from traveling along the axon and from maturing, leaving the cell with no means to clear broken-down mitochondria.
Researchers have used mass spectrometry to catalog and quantify five types of tau modification in wild-type and transgenic mouse models of AD. While their results suggest little if any difference between normal and plaque-ridden mice, they do reveal previously unknown modifications, and may provide new clues to the protein’s normal function. Other scientists praised the rigor and breadth of the work and its importance for future research. Read the story and extensive commentary.
Using an optical gadget that can be fitted to any two-photon microscope, researchers have been able to look through the skull into the mouse brain. They used a specialized mirror to straighten wayward light rays scattered by the cranium and see shape-shifting microglia and tiny dendritic spines. While the imaging technique does not probe quite as deep as light shone through a cranial window or through a thinned skull, it allows researchers to glimpse the brain’s business without disrupting it.
Neurons in Alzheimer’s disease patients accumulate swollen, dysfunctional endosomes. A new report now directly links the β C-terminal fragment of APP to this pathology. The fragment recruits a protein that keeps endosomes active, causing accelerated endocytosis and potentially stressing protein degradation pathways.
Data-heads are racing to get a handle on ALS progression in the DREAM ALS Stratification Prize4Life Challenge sponsored by the ALS charity Prize4Life, Sage Bionetworks, and DREAM Challenges. Mining data from 17 previous trials, entrants hope to group patients with similar disease trajectories, then use their shared characteristics to develop an algorithm that predicts disease course. Winning teams will receive $7,000 and the opportunity to pen a paper that Nature Biotechnology will consider for publication. The real winners could be patients and organizers of clinical trials, who might use the algorithms to design more efficient and cost-effective studies. Registration is still open. Submissions are due by September 22.
- Kun Ping Lu on Inventory of Tau Modifications Hints at Undiscovered Functions
- Li Gan on Inventory of Tau Modifications Hints at Undiscovered Functions
- Dirk Beher on Inventory of Tau Modifications Hints at Undiscovered Functions
- Fred Van Leuven on Inventory of Tau Modifications Hints at Undiscovered Functions
- Khalid Iqbal, Fei Liu and Cheng-Xin Gong on Inventory of Tau Modifications Hints at Undiscovered Functions
- Peter Davies on Inventory of Tau Modifications Hints at Undiscovered Functions
- Diane Hanger on Inventory of Tau Modifications Hints at Undiscovered Functions