Across Time and Space: Machine Learning Reveals Paths to Dementia
Analysis of MRI brain volume data identifies multiple AD and FTD/ALS disease subtypes with distinct patterns of degeneration over time.
NEWS
High-Resolution Map of Hippocampus Reveals Multiple Subnetworks
The most detailed look yet at hippocampal wiring may guide future functional studies and disease research.
ALS on a Chip—A Model for Screening Therapeutics?
Neuromuscular junctions between human stem cell-derived motor neurons and skeletal muscle fibers faltered when cells came from an ALS patient.
Crystal Structure of Aβ and Proposed Receptor Solved
A small molecule that protects neurons fends off a short region of Aβ from a specific pocket on the LilrB2 receptor.
Mixed Messages: mRNA Splicing Errors May Promote Alzheimer’s
A large-scale expression study finds mis-splicing of a specific set of genes in AD brain that includes several known risk genes.
Intelligence Matters More for Brain Reserve, but Education Helps
Longitudinal and genetic studies reveal that intelligence underlies cognitive reserve.
Sans Synuclein Tetramers, Mice Mimic Parkinson’s Disease
Mutations that destabilize α-synuclein tetramers leave young mice with severe and progressive motor problems resembling those of PD.
Noncoding RNAs Evince World of Gene Regulation in Dopaminergic Neurons
Using TNEs—snippets of RNA transcribed from noncoding regions—as a gauge of enhancer activity, researchers tied Parkinson’s risk variants to gene regulation.
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Alzforum has launched a Virtual Exhibit Hall, a place for companies to showcase their initatives, products, and services. We welcome our exhibitors - Biogen, BioLegend, NanoString Technologies, Inc., and The Jackson Laboratory and encourage our readers to explore their virtual booths here.
SPOTLIGHT
Disentangling Dementias
A new machine-learning technique identifies three subtypes of Alzheimer’s disease and four of frontotemporal dementia based on their unique patterns of brain atrophy over time. In FTD, the subtypes tracked with disease-causing genetic mutations, while in AD, the three major subtypes helped predict the risk of clinical progression from mild cognitive impairment to dementia. The method, which the authors call SuStaIn, for Subtype and Stage Inference, could help with selection of candidates for clinical trials, and eventually with precision-medicine approaches to dementia.
High-Resolution Map of Hippocampus Reveals Multiple Subnetworks
Get ready to rethink the hippocampus. Under detailed, cellular-level analysis of gene expression and axonal tracts, its six anatomical parts subdivide into 22 distinct regions, each with a unique pattern of connectivity to other hippocampal regions and the rest of the brain. The data will provide researchers with new tools to investigate hippocampal function in health and disease.
Mixed Messages: mRNA Splicing Errors May Promote Alzheimer’s
Add mRNA splicing to the list of what goes awry in AD brain. In a study of 450 postmortem AD and control brains, the amount of neuropathology correlated with alternative splicing or mis-splicing of a small set of transcripts. For some of these transcripts, AD-associated genetic variants correlated with the mis-splicing, hinting at a role for splicing errors in disease pathogenesis.
PD Mouse Model Puts Spotlight on α-Synuclein Tetramers
The theory that destabilization of physiological tetramers contributes to α-synuclein proteotoxicity was put to the test in mice engineered with mutations that break up the multimers. The animals developed severe movement disorders at an early age. Whole-body tremor and L-DOPA responsiveness, worse in males, were reminiscent of Parkinson’s disease.
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