Daily Archives: January 11, 2021

Alzheimer’s Is Actually 3 Distinct Disease Subtypes

Alzheimer’s Disease (AD) is probably more diverse than our traditional models suggest. Postmortem, RNA sequencing has revealed three major molecular subtypes of the disease, each of which presents differently in the brain and which holds a unique genetic risk.  Such knowledge could help us predict who is most vulnerable to each subtype, how their disease might progress and what treatments might suit them best, potentially leading to better outcomes. It could also help explain why effective treatments for AD have proved so challenging to find thus far.

The mouse models we currently have for pharmaceutical research match a particular subset of AD,  but not all subtypes simultaneouslyThis may partially explain why a vast majority of drugs that succeeded in specific mouse models do not align with generalised human trials across all AD subtypes,”  say the authors. “Therefore,” the authors conclude, “subtyping patients with AD is a critical step toward precision medicine for this devastating disease.

Traditionally, AD is thought to be marked by clumps of amyloid-beta plaques (), as well as tangles of tau proteins (NFTs) found in postmortem biopsies of the brain. Both of these markers have become synonymous with the disease, but in recent years our leading hypotheses about what they actually do to our brains have come under question. Typically, accumulations of and NFT are thought to drive neuronal and synaptic loss, predominantly within the cerebral cortex and hippocampus. Further degeneration then follows, including inflammation and degeneration of nerve cells‘ protective coating, which causes signals in our brains to slow down.

Strangely enough, however, recent evidence has shown up to a third of patients with a confirmed, clinical diagnosis have no Aβ plaques in postmortem biopsies. What’s more, many of those found with plaques at death did not show cognitive impairment in life. Instead of being an early trigger of AD, setting off neurodegeneration and driving memory loss and confusion, in some people, Aβ plaques appear to be latecomers. On the other hand, recent evidence suggests tau proteins are there from the very earliest stages.

In light of all this research, it’s highly likely there are specific subtypes of AD that we simply haven’t teased apart yet. The new research has helped unbraid three major strands. To do this, researchers analysed 1,543 transcriptomes – the genetic processes being express in the cellacross five brain regions, which were collected post mortem from two AD cohorts.

Source: https://advances.sciencemag.org/

Single Dose Nanoparticle Vaccine Efficient To Produce Covid Antibodies

Across the world, health care workers and high-risk groups are beginning to receive COVID-19 vaccines, offering hope for a return to normalcy amidst the pandemic. However, the vaccines authorized for emergency use in the U.S. require two doses to be effective, which can create problems with logistics and compliance. Now, researchers reporting in ACS Central Science have developed a nanoparticle vaccine that elicits a virus-neutralizing antibody response in mice after only a single dose.

The primary target for COVID-19 vaccines is the spike protein, which is necessary for SARS-CoV-2’s entry into cells. Both of the vaccines currently authorized in the U.S. are mRNA vaccines that cause human cells to temporarily produce the spike protein, triggering an immune response and antibody production.

Peter Kim and colleagues wanted to try a different approach: a vaccine consisting of multiple copies of the spike protein displayed on ferritin nanoparticles. Ferritin is an iron storage protein found in many organisms that self-assembles into a larger nanoparticle. Other proteins, such as viral antigens, can be fused to ferritin so that each nanoparticle displays several copies of the protein, which might cause a stronger immune response than a single copy.

The researchers spliced spike protein and ferritin DNA together and then expressed the hybrid protein in cultured mammalian cells. The ferritin self-assembled into nanoparticles, each bearing eight copies of the spike protein trimer. The team purified the spike/ferritin particles and injected them into mice. After a single immunization, mice produced neutralizing antibody titers that were at least two times higher than those in convalescent plasma from COVID-19 patients, and significantly higher than those in mice immunized with the spike protein alone. A second immunization 21 days later produced even higher antibody levels. Although these results must be confirmed in human clinical trials, they suggest that the spike/ferritin nanoparticles may be a viable strategy for single-dose vaccination against COVID-19, the researchers say.

Source: https://www.acs.org/