Stroke Severity, Recurrence Increase Dementia Risk
Dementia risk nearly doubled after each minor stroke and tripled after each major one, regardless of vascular risk factors. Risk climbed almost sevenfold after multiple major strokes.
NEWS
Survey of Tau Partners Highlights Synaptic, Mitochondrial Roles
An unbiased “interactome” generated from human neurons could shed light on what goes wrong in tauopathies, and help identify new therapeutic targets.
Neuron-Specific Retromer Identified—Does It Stave Off Alzheimer’s?
When this retromer faltered in mice, Aβ levels rose in the brain and synaptic signaling waned in the transentorhinal cortex. General retromer loss in hippocampal neurons evoked dystrophic microglia similar to those seen in AD.
New PET Tracer Binds Muscarinic Acetylcholine Receptors
MK-6884 measures allosteric changes to the M4 subtype of muscarinic receptors in people and in monkeys. Ligand binding tightened when people took donepezil, an acetylcholinesterase inhibitor.
Identical Twins Share Tau Trajectory, but Lifestyle Can Make a Difference
Among 39 sets of identical twins, tau tangles accumulated in a strikingly similar pattern within each pair. A pair's discordance was due to Aβ and factors such as exercise.
CMS Plans to Limit Aduhelm Coverage to Clinical Trials
The decision will curtail access until efficacy is shown. Many Alzheimer’s researchers call it a reasonable compromise, others question how it will work in practice.
2021—A Turning Point for Alzheimer’s Research and Therapy?
Alzforum editors review the highlights of last year’s clinical and research developments.
In Frontotemporal Dementia Model, Do Riled-Up Microglia Help?
Progranulin deficiency hyperactivates microglia, but calming these cells worsened synapse loss and neurodegeneration in mice.
Virtual Exhibit Hall
Alzforum encourages users to visit the Virtual Exhibit Hall, where companies showcase their newest initiatives, products, and services. We welcome F. Hoffmann-La Roche, joining our other exhibitors — Biogen, BioLegend, Abcam, BrainXell, and the Jackson Laboratory.
SPOTLIGHT
Survey of Tau Partners Highlights Synaptic, Mitochondrial Roles
Tau was originally thought of as a microtubule-binding protein, but it seems to be more of a jack-of-all-trades. A comprehensive survey of the tau “interactome” in human neurons finds tau consorting with proteins at the synapse, nucleus, ribonucleosome, lysosome, and—surprisingly—mitochondria. Mutant tau lost these mitochondrial interactions, and that loss correlated with less energy production. Researchers said this interactome offers a trove of data to mine for disease mechanisms and new therapeutic targets.
Neuron-Specific Retromer Identified—Does It Stave Off Alzheimer’s?
Can retromer malfunction set the stage for cellular changes seen in Alzheimer’s disease? Two recent papers suggest as much. In one, deleting the neuron-specific retromer protein VPS26b stymied glutamate receptor recycling and synapse signaling only in the mouse transentorhinal cortex, a region affected early on by AD pathology. In another, mice lacking another retromer protein, VPS35, in their hippocampal neurons had endosomal traffic jams in their neurons, and their microglia resembled those seen in AD. Adding VPS35 back into the neurons normalized protein trafficking and the microglia.
New PET Tracer Binds Muscarinic Acetylcholine Receptors
Researchers have a new tool for measuring changes in neurotransmission in living people. The new PET tracer, MK-6884, targets the M4 subtype of muscarinic cholinergic receptors. The ligand nuzzles into an allosteric pocket, latching on more tightly in the presence of higher acetylcholine concentrations, such as when people take the acetylcholinesterase inhibitor donepezil. People with Alzheimer’s bound less ligand. MK-6884 opens the door for scientists to measure cholinergic drug efficacy and the neuropathological loss of acetylcholine receptors in AD and other diseases.
Same Genome, Same Tau?
Shared genetics not only makes twins look identical; as it turns out, it also makes their tau accumulation remarkably similar. Based on PET scans from 94 monozygotic twin pairs, both the magnitude and spatial distribution of neurofibrillary tangles was found to be more alike within twin pairs than it was among age-matched participants. However, genes weren’t everything. Where tau patterns differed in twins, a healthier lifestyle correlated with lower burden.
CMS Plans to Limit Aduhelm Coverage to Clinical Trials
In the latest plot twist in the aducanumab saga, Medicare has said it intends to cover the drug—and other anti-amyloid antibodies to come—only in clinical trials approved by the CMS or the NIH. While advocacy groups are furious, many AD researchers call this a reasonable compromise. However, they question whether these trials are feasible, and object to treating all antibodies as a class. A final decision by CMS is expected in April. Read Alzforum’s coverage of this complicated issue, and 35 comments from experts across the field.
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