A birth cohort study in New York City finds a sharp drop in dementia incidence in people born after 1929. Neither better cardiovascular health nor more education explain the data.
Autophagy spares motor neurons from synaptic ruin early in disease, but stokes the fires of neuroinflammation later on.
Engineering mice to express a tagged polyA-binding protein in specific cell types allows researchers to pull out neuronal, astroglial, or microglial mRNAs from the intact brain and examine each cell type′s mix of mRNA 3' ends.
RIPK1 catapults microglia into an inflammatory frenzy, disrupting their lysosomal pathway and undermining Aβ clearance. A new drug target?
Two new mouse studies show that a ketogenic diet that avoids obesity improves the health of mind and body, increasing median lifespan. Related studies hint at possible benefits for Alzheimer’s disease.
CryoEM reveals high-resolution view of full length of Aβ42 in a novel conformation.
Liquid droplets of tau subsume and concentrate tubulin, which then rapidly forms microtubules.
Dopaminergic neurons made from human iPS cells take root in monkey brains and reverse PD-like motor problems. Matching donor and host immune signatures mitigates graft rejection.
In Alzheimer’s disease, microglia change from Aβ-eating machines into cells without much of an appetite. What causes this shift? One suspect is the RIPK1 kinase, which microglia express in response to inflammatory signals. According to new research, RIPK1 stalls Aβ breakdown by crippling the lysosomal machinery, and blocking the enzyme reduces plaques in AD model mice and improves their memory. The results point to a possible new treatment target for Alzheimer’s and related disorders. More broadly, the study characterizes RIPK1-dependent pathways in microglia.
Two independent studies report that a high-fat, low-carb regimen, known as the ketogenic diet, preserves memory and physical fitness in old mice. The diet also nudged up median lifespan, upping PPARα signaling and reducing mTOR signaling, changes previously tied to lifespan extension. Could this unpalatable diet, or supplements that boost ketone bodies, help people with Alzheimer’s?
The most detailed structure of an Aβ fibril to date introduces a new twist on protofibril pairing, and a novel dimer interface. Improved cryoEM, trained on a stable, homogenous fibril, allowed researchers resolve all the residues in a synthetic fiber of Aβ42. The hope is that before too long, researchers will get a look at physiological amyloid from diseased brain in similar detail.
Liquid droplets of tau catalyze the rapid growth of microtubules, according to a new biophysical study. As in other recent papers, researchers found that tau undergoes liquid-liquid phase separation, but when they added tubulin to the mix, microtubules rapidly polymerized and bundled together, drastically squeezing their droplet chambers into elongating "shooting stars." Commentators praised the beauty of the in vitro results, yet wondered if they reflect real biology in the human brain. Watch the videos.
- Robert Tycko on Amyloid-β Fibril Structure Bares All
- Walter A. Rocca on More Evidence that Dementia Case Numbers Are Falling
- Sudha Seshadri on More Evidence that Dementia Case Numbers Are Falling
- Johnathan Cooper-Knock on From Protector to Instigator, Autophagy Makes About-Face in ALS
- Claudio Hetz on From Protector to Instigator, Autophagy Makes About-Face in ALS
- Marie-Eve Tremblay on Microglial Kinase Promotes DAM, Blocks Lysosomal Aβ Digestion
- Elena Galea on Microglial Kinase Promotes DAM, Blocks Lysosomal Aβ Digestion
- Steven Finkbeiner on Microglial Kinase Promotes DAM, Blocks Lysosomal Aβ Digestion
- Thomas Beach on Retinal Plaques May Enable Noninvasive Screening for AD
- Ullrich Wuellner on Asthma Drugs Suppress α-Synuclein, Reduce Parkinson’s Risk
- Markus Zweckstetter on Protein Liquid-Liquid Phase Transitions: The Science Is About to Gel
- Kenneth Kosik on Tau Droplets Sprout Microtubules
- Jurre den Haan on Retinal Plaques May Enable Noninvasive Screening for AD
- Mark Frasier on Asthma Drugs Suppress α-Synuclein, Reduce Parkinson’s Risk
- Tuan Leng Tay on Somatic SNAFU—Can a Few Mutant Microglia Cause Neurodegenerative Disease?
- Lindsay Farrer on New Look at Sex and ApoE4 Puts Women at Risk Earlier than Men
- Eric M. Reiman on New Look at Sex and ApoE4 Puts Women at Risk Earlier than Men
- G. William Rebeck on New Look at Sex and ApoE4 Puts Women at Risk Earlier than Men
- A. Claudio Cuello on Does Lithium in Tap Water Keep Dementia at Bay?
- Ari Waisman on Long Live the Microglia! Studies Trace Their Lifespans in Mice and Humans
- Christian Haass on Long Live the Microglia! Studies Trace Their Lifespans in Mice and Humans