Dying neurons trigger a transcriptional change in microglia that requires APOE and TREM2. Does this altered phenotype fight or fuel disease?
A surprising fold emerges from a low-complexity domain. Videos show core holding steady, N and C termini dancing around.
Multiple lines of new evidence are tying disparate cellular neurodegenerative pathologies together. One result: The FTD risk factor progranulin is now firmly placed in lysosomes.
Tau in the plasma rises after traumatic brain injury, with cognitive decline, and progression to mild cognitive impairment.
ApoE, especially E4, interacts directly and indirectly with tau. This worsens outcomes along the pathogenic process, from soluble tau to glial activation and brain atrophy. All without Aβ.
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.
Low-complexity (LC) domains mediate protein-protein interactions that lead to phase separation of proteins into liquid-like droplets. Just how these unstructured domains might come together is unclear. Now a new study suggests reversible amyloids may play a role. An NMR structure of FUS-LC fibrils reveals a cross-β core held together by relatively weak forces. Phosphorylation of residues within the fibril core prevents liquid droplet formation by FUS-LC.
Part of the cell’s garbage disposal system, these organelles get stopped up in many neurodegenerative diseases. Now research paints the lysosomal system as a central hub of dysfunction in PD, where pathological cascades that include oxidative stress, excess α-synuclein, and lipid metabolism converge and interact. Separate research defines a lysosomal role for progranulin, a major genetic risk factor for familial and sporadic FTD. Together, the findings sharpen interest in targeting lysosomes therapeutically.
Despite being identified as an Alzheimer’s risk factor as far back as 1993, ApoE has not given rise to new therapeutics. Might that change with a new report that characterizes ApoE’s effect on tau? The study claims that, starting with accumulation of soluble tau, the presence of ApoE, especially its E4 version, exacerbates every major step along the pathogenic cascade. Axonal tau redistribution to neuronal soma, neurodegeneration and atrophy, micro- and astroglial activation—for all those measures, lack of ApoE was strangely protective, ApoE was bad, ApoE4 worst. ApoE carriers with non-Aβ tauopathies had more regional neurodegeneration, and E4 homozygote people with mild AD progressed faster.
- Christopher Glass on ApoE and Trem2 Flip a Microglial Switch in Neurodegenerative Disease
- Julie Forman-Kay on Out of Chaos, Order: Reversible Amyloid Structure Seen in Phase Separation
- John Hardy on Lysosomes Take Center Stage in Parkinson’s and Frontotemporal Dementia
- Thomas Kukar and Christopher Holler on Lipidomic and Transcriptomic Basis of Lysosomal Dysfunction in Progranulin Deficiency.
- Li Gan on Lipidomic and Transcriptomic Basis of Lysosomal Dysfunction in Progranulin Deficiency.
- Chris Lee on Lipidomic and Transcriptomic Basis of Lysosomal Dysfunction in Progranulin Deficiency.
- Holger Wille on Amyloid-β Fibril Structure Bares All
- 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