Gaining a Foothold: Amyloid Immunotherapy in Clinical Practice
Lecanemab will soon have maintenance dosing and subcutaneous formulations available; FDA advisory committee will consider donanemab June 10.
Lecanemab will soon have maintenance dosing and subcutaneous formulations available; FDA advisory committee will consider donanemab June 10.
An adeno-associated virus that binds the transferrin receptor delivered β-glucocerebrosidase throughout the mouse brain.
APOE4 carriers who also have a glycine to glutamic acid substitution in the extracellular matrix protein were 71 percent less likely to develop Alzheimer’s disease.
Blood and other in vitro assays will need to meet the same standards as medical devices, including demonstrating diagnostic accuracy.
By age 65, nearly all people who carry two copies of APOE4 harbor neuropathological or biomarker evidence of AD pathology.
In mice and cultured human neurons, PLCγ2 knockdown thinned out synapses and suppressed neuron firing. Rare loss-of-function PLCγ2 variants hike AD risk 10-fold.
People who had a damaged locus coeruleus accumulated tangles in their medial temporal lobes over the next three years, and their cognition declined.
Known for shuttling APP, the endosomal receptor latches on to tau. Knocking it down in glia reduced tau seeding. The N1358S risk variant ramped it up.
Scientists have co-opted the transferrin receptor to ferry enzymes, antibodies, and other potential therapeutics into the brain. Now, they have done the same for viruses. Targeting an adeno-associated virus to the transferrin receptor boosted viral delivery into the mouse brain by 30-fold. The virus expressed β-glucocerebrosidase throughout the brain. This modified virus might improve the efficiency of gene therapy.
APOE4 is the strongest genetic risk factor for sporadic AD. Yet some carriers evade the disease entirely. How? By having rare protective variants in other genes, say scientists. Among 510 such rare coding mutations, one in the gene for fibronectin reduced AD risk in APOE4 homozygotes by 71 percent. Those who did develop AD got symptoms 3.5 years later than non-variant carriers. Cognitively healthy APOE4 carriers had less gliosis and fibronectin surrounding blood vessels in the brain than did those with AD.
A new study argues that APOE4 homozygosity represents a genetically determinant form of AD, as opposed to a mere risk factor. By age 65, most people with two copies of the variant have amyloid plaques brewing in their brain. The authors believe APOE4 homozygotes should be considered similar to people with autosomal-dominant forms of AD. Others disagree.
Autopsy studies suggest that neurofibrillary tangles first appear in the locus coeruleus (LC) of the brainstem. Now, a longitudinal imaging study lends support to that theory. LC degeneration on MRI, a proxy for tangles, precedes tau PET positivity in the medial temporal lobe, and poor cognition, by three years.
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