Frontal Metabolic Patterns Mark Behavioral Subtype of AD
Hypometabolism in the frontal cortex and in the anterior default mode network distinguish the behavioral variant of AD from typical AD.
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Adenosine Receptors Rev Up Immune Response, Memory Loss, in Tau Model
Overexpressing neuronal A2A receptors stoked C1q in microglia, damaging synapses and memory.
In Tauopathy, ApoE Destroys Neurons Via Microglia
Ablating the immune cells protected mouse models of frontotemporal dementia from the neurodegeneration caused by human ApoE4.
Right Turn: Aβ Fibril Structure from Alzheimer’s Brain Reveals Surprising Twist
The first ever cryoEM structures of Aβ fibrils extracted from AD tissue look quite different than prior structures of fibrils generated in vitro. For starters, they are right-hand twisted, not left-hand.
ApoE4 and Tau in Alzheimer’s: Worse Than We Thought? Especially in Women
Imaging studies suggest that ApoE4 carriers may be more susceptible to the effects of tangles, particularly if they are women.
Attack of the Clones? Memory CD8+ T Cells Stalk the AD, PD Brain
The cells are primed to attack. Their targets include Epstein-Barr virus peptides.
With a Shot of Adrenaline, Amyloid-β Sparks Tau Cascade
Aβ oligomers latch onto adrenergic receptors, mobilizing a kinase that phosphorylates tau. Blocking adrenergic signaling wards off memory problems in amyloidosis mice.
Connectivity, Not Proximity, Predicts Tau Spread
Functional connections between two brain regions are the strongest indicator that pathologic, accumulated tau will spread from one to another.
Ruffles and Sphincters Control the Spigot of Fresh Blood in the Brain
Two studies reveal new aspects of the neurovascular physiology that regulate the flow of oxygenated blood into the brain’s arterioles and capillaries in response to neuronal stimulation.
Stress-Associated Protein Modulates γ-Secretase to Make More Aβ
Under diabetic conditions, SERP1 binds secretase subunit, cranking up cleavage of APP but not Notch. The finding offers a mechanistic link between diabetes and Alzheimer’s.
Sigh of Relief? Lung Effects of LRRK2 Inhibitors are Mild.
In nonhuman primates, three classes of LRRK2 kinase inhibitor cause microscopic changes in lung morphology, but they are reversible and do not impair breathing. Parkinson’s programs remain on track.
Could Tau PET Replace Amyloid Biomarkers as a Diagnostic for AD?
A large, cross-sectional study finds that RO-948 PET discriminates AD dementia from other disorders more accurately than do CSF biomarkers or MRI.
Gut Microbes: The Difference Between Life and Death in C9ORF72 Mice
Harvard or MIT? The microbiomes of mice raised in different facilities dictated their response to C9 deficiency, including whether they died young. Do gut microbes influence ALS?
Molecular Transport Vehicle Shuttles Therapies into Brain
Built to cross the blood-brain barrier, the vehicle delivers therapeutic antibodies, enzymes, and potentially small molecules such as oligonucleotides.
In the Wake of COVID-19: Trials Interrupted, Delayed, Cancelled
Many Alzheimer’s trials had minimal dosing interruptions, but recruitment stopped for a time. Others trials fared worse, with some scrapped altogether. One administered study drug in an ambulance.
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