They discover that Alzheimer’s human proteins damage more

Group researchers Alzheimer’s disease neuropathology (Neuroad) of Ibima Bionand platform, which leads Antonia Gutiérrez Pérezwith participation of Department of Cellular Biology, Genetics and Physiology of the University of Malaga (UMA) and of Institute for Memory Impairments and Neurological Disorders From the University of California, Irvine have discovered that the proteins that cause Alzheimer’s propagate differently depending on whether they come from human brains or mouse models.

According to the study principal of the study, David Baglietto, “Understand the peculiarities of pathogenic seeds brings us closer to more precise treatments and adapted to each Alzheimer’s variant”. The next step will be to explore how to modify or neutralize these seeds by antibodies or small compounds, they have reported from Ibima in a note.

Alzheimer’s disease, which affects almost 50 million of people worldwide and whose figure is expected to be doubled by 2050, is characterized by the accumulation of two poorly folded proteins which, when unfolding anomalously, act as they act as they act as “seeds” that capture their healthy versions and make them pathological copies.

This propagation process explains the expansion of injuries to different regions of the brain, although so far it was not understood why human seeds and those of other mammals behave differently. “Understanding how these” seeds “propagate is essential to unravel the complexity of the Alzheimer’s and find ways to stop its progress”They have highlighted.

The research group, led by David Baglietto and Juana Andreo Lópezhas carried out a crucial study to address this issue. To do this, they injected brain extracts from patients with Alzheimer’s and Model Modified Modified Modified Modified in the Living Mouse Hippocampus.

As explained, The objective of the study It was to determine whether human or murin “seeds” were more likely to convert healthy proteins into their pathological copies, as well as establishing possible differences in the response of immune cells of the brain to this pathology.

Thus, they have pointed out that “The study results have revealed a complex panorama and, in some aspects, unexpected”. It was observed that human brain extracts with Alzheimer’s inoculated in mice brains demonstrated a remarkably more aggressive capacity compared to those who received mouse extracts.

In this regard, they have specified that this greater power of the human “seeds” was confirmed when calculating the activity of aggregation of the samples, observing greater activity in human samples with respect to mouse.

“Our data indicates that Alzheimer’s” seeds “of human origin possess different propertieswhich facilitates the formation of amyloid aggregates in a more efficient way than mouses, “explain the researchers in the article.

This suggests that human “seeds” could have different structural conformations or “strains” with unique pathogenic properties, which would help explain the clinical heterogeneity observed in Alzheimer’s patients.

An unpublished experiment with human brain tissue

To shed light on this enigma, a consortium of Spanish and North American researchers, led from Ibima Bionand Platform and the Department of Cell Biology, Genetics and Physiology of the Uma and in collaboration with the Institute for Memory Impairments and Neurological Disorders From the University of California, Irvine, he designed an unpublished experiment consisting of the extraction of brain tissue of patients who died with Alzheimer’s.

These samples later They were inoculated in key areas of the brain of live miceand after months of incubation they quantified and studied the inflammatory response, highlighting the role of microglia, that is, the “barrier cells” in charge of surrounding and isolating the damage. Microglia, understood as the “guardians” or “immune cells” of the brain, usually grouped to limit neuronal damage.

After injecting mouse seeds, the researchers observed a much weaker microglial response and an increase in neuritic damage and the phosphorylated tau adjacent to these naked plates. In vitro cell crops experiments revealed that Murinas also were more toxic than humansuggesting a state of “exhaustion” that compromises the protective function of these cells.

To approach the sporadic Alzheimer’s –95% of cases-, studied a new mouse model without family mutations, and after 18 months of exposure to human seeds, amyloid plaques did not appear, although an increase in structures associated with failures in the elimination of brain waste and early neurodegenerative processes.

This suggests that Sporadic Alzheimer may require multiple additional factors or even more prolonged incubation periods, they have stated in the statement.

As they have pointed out, this work contributes “Several key lessons”as inter-species differences. And it is that “not all animal models faithfully reproduce human pathology, which is vital to design effective therapies,” they explained.

In addition, it leads to microglia as a therapeutic objective. “Promising the function of these cells could slow down the progression of the disease“; and in reference to early detection, it suggests that initial biomarkers can be analyzed before plaque formation, opening the door at earlier interventions.