New potential immunotherapies and insight into single-cell responses were highlights of a small meeting in Denmark.
Research on postmortem human brain strengthens the idea that an ebbing of neurogenesis may underlie cognitive decline.
Thousands of stretches of the genome go undetected by standard short-read sequencing techniques. Unmasking these “dark regions” revealed a potential AD risk variant in the CR1 gene.
Using single-nuclei or cell sorting, three separate research groups sequenced RNA from human postmortem brains. They unveiled AD-associated gene-expression signatures, but disease-related transcriptomes from human microglia were quite different from those in mice.
Data on ASOs, presented recently at the annual meeting of the American Academy of Neurology, depict RNA-based therapies as broadly on the rise in neurodegenerative diseases.
In a new, inducible mouse model, poly(GR) damages mitochondria, but its effect is reversible. In flies, turning off transcription of hexanucleotide expansion protects cells.
Expression of VCAM1 on the endothelial cells that line the blood-brain barrier allowed aging factors in the plasma to exact their toll on the brain.
Lanabecestat, elenbecestat, and umibecestat all showed data at the AD/PD conference in Lisbon. Learn what definitely doesn’t work and what might yet.
Virtual Exhibit Hall
Alzforum encourages users to visit the Virtual Exhibit Hall, where companies showcase their newest initiatives, products, and services. We welcome Dash Genomics, Inc. and Abcam, which join our other exhibitors — Biogen, BioLegend, BrainXell, NanoString Technologies, and the Jackson Laboratory.
This year, FENS chose Alzheimer’s disease as the topic for the first of its biannual brain conferences. Called “Understanding and treating Alzheimer’s disease,” the conference came a year after its sponsor Lundbeck awarded the Brain Prize to four stalwarts in AD research: Bart De Strooper, Michel Goedert, Christian Haass, and John Hardy. Co-chaired by Haass and Beth Stevens, the meeting, held north of Copenhagen, fused discussions of Aβ and tau neuropathology with deliberations on cutting-edge single-cell transcriptomics and glial biology. Read Tom Fagan’s highlights of the meeting.
Myriad studies place microglia front and center in AD pathogenesis, yet figuring out exactly what the immune cells are doing in the AD brain is a tall order. Three recent studies have taken a stab at uncovering transcriptomic signatures of microglia in postmortem AD brain samples, reporting that transcriptomes of human Alzheimer’s microglia (HAM) bear little resemblance to disease-associated microglia (DAM) of mouse models. Despite differences, some important similarities emerged, including a rise in ApoE and age-associated genes.
Two studies uncover new players in C9ORF72 toxicity, and suggest ways to shut them down. Scientists know that the most common genetic cause of ALS and FTD, C9ORF72 hexanucleotide repeats, generate toxic RNAs and a raft of dangerous dipeptides. Now a mouse model reveals that, even at low levels, the poly(GR) dipeptide poisons mitochondria, but the damage is reversible when caught early. The second study sheds new light on the specialized transcription machinery cells use to generate RNA from the repeat, suggesting new targets to choke off production at its roots.
We have concluded coverage from the 14th AD/PD conference held earlier this spring in Lisbon, Portugal. Our 16-part series runs the gamut from genetics to innate immune cells, from ApoE to lipids, from the search for diagnostic tests to the basic science of endocytosis and α-synuclein. We covered the pursuit of new therapeutic targets, as well as the painful harvest currently being reaped from Phase 3 anti-amyloid trials. On that, scientists at different companies were sharing detailed results from each other’s programs in hopes of learning as they "fall forward toward success." Crenezumab, lanabecestat, aducanumab are the latest official casualties; AD/PD offered data on the first two. Despite obituaries in the analyst press, the amyloid hypothesis is not dead. Gantenerumab, BAN2401, elenbecestat, umibecestat, and CAD106 are in late-stage trials, and crenezumab and solanezumab are still being evaluated in presymptomatic AD. See AD/PD Parts 15, 16.
- Anne-Sophie Hafner on Plasticity Hums With Protein Synthesis on Both Sides of Synapse
- Jason Ulrich on When it Comes to Alzheimer’s Disease, Do Human Microglia Even Give a DAM?
- Elizabeth Bradshaw on Alzheimer’s patient brain myeloid cells exhibit enhanced aging and unique transcriptional activation
- Laura Ranum on C9ORF72-ALS/FTD-associated poly(GR) binds Atp5a1 and compromises mitochondrial function in vivo.
- Robert Baloh on C9ORF72-ALS/FTD-associated poly(GR) binds Atp5a1 and compromises mitochondrial function in vivo.
- Adrian Isaacs on C9ORF72-ALS/FTD-associated poly(GR) binds Atp5a1 and compromises mitochondrial function in vivo.
- Ludo Van Den Bosch on C9ORF72-ALS/FTD-associated poly(GR) binds Atp5a1 and compromises mitochondrial function in vivo.
- Heinz Hillen on BACE Inhibitors: Postmortem on One, Live Updates on Two
- Dante Marciani on Keep Your Enthusiasm? Scientists Process Brutal Trial Data
- Celia Williams on Plasticity Hums With Protein Synthesis on Both Sides of Synapse
- Marvin Berman on Gamma Waves Synchronized by Light: Good for Synapses, Memory?
- Christos Proukakis on Single-cell transcriptomic analysis of Alzheimer's disease.
- Ulrich Hengst on Plasticity Hums With Protein Synthesis on Both Sides of Synapse
- John Breitner on Antibodies Against Microglial Receptors TREM2 and CD33 Head to Trials
- Logan Schneider on Drug Reported to Help Alzheimer’s Patients Sleep Better
- Tim Bartels on Forget Fibrils: Lewy Pathology Is More Lipid Than Protein
- Tiago Outeiro on Forget Fibrils: Lewy Pathology Is More Lipid Than Protein
- Gil Rabinovici on Longitudinal Tau-PET Links Aβ to Subsequent Rise in Cortical Tau
- Ruth Itzhaki on On The Docket at AD/PD: The Many Crimes of ApoE4
- Brian Draper on Amyloid-PET Results Lead Some to Ponder Assisted Death in Future
- Joshua Grill on Amyloid-PET Results Lead Some to Ponder Assisted Death in Future