Find signs of why Alzheimer's is stronger in women

Find signs of why Alzheimer’s is stronger in women


New research uncovered biological clues about why Alzheimer’s is more common in women than in men and how the most common form of dementia varies between the sexes.

Scientists at the international conference of the Alzheimer’s Association, which takes place in Los Angeles, presented evidence that evil diffuses differently in the brain of women than in men. They also identified sex-specific genes that appear to be related to the risk and progression of the disease.

Two-thirds of people living with Alzheimer’s in the United States are women, and this is not only because they are longer-lived than men, but the specialists also pointed out.

Previous studies indicate that the probability of suffering from the disease is more significant in women than in men, regardless of age, which suggests that biological differences also have a role.

On the other hand, Spanish researchers identified a mechanism in the pathogenesis of the disease, which is altered in these patients and increases significantly in the brain and cerebrospinal fluid.

The work, published in Nature Neuroscience, led by researchers from the Severo Ochoa Molecular Biology Center CSIC-Autonomous University of Madrid, Paola Bovolenta and PilarEsteve, was carried out in collaboration with other centers and was funded by the Tatiana Pérez de Guzmán Foundation. Good.

In their work, they demonstrated that the protein SFRP1 (Secreted-Frizzled-Related-Protein-1) plays a fundamental role in the toxic cascade that leads to the accumulation of amyloid peptides in the brains of Alzheimer’s patients and the development of other brands. Characteristics of this disease.

It also shows that the level of SFRP1 is altered in these patients and increases significantly in the brain and cerebrospinal fluid. The excess of that protein accumulates in the amyloid plaques, where it binds to beta-amyloid peptides. In addition, levels of it correlate positively with those of soluble beta-amyloid peptide.

The work, whose first author is Esteve, suggests that the increase in the levels of SFRP1 in the brain could be the cause of an increase in the toxic processing of the amyloid precursor protein and its accumulation, as well as other brain alterations that include synaptic dysfunction and inflammation of that organ, characteristic of the disease.

Crucial protein

“Our work reveals that SFRP1, crucial in the pathogenesis of the disease, is a promising therapeutic objective,” said Bovolenta. He pointed out that the next step will be to carry out a longitudinal study to analyze if the levels of that protein in blood can predict the disease before the symptoms manifest, which would allow obtaining a marker for early diagnosis.

The results obtained in this work convert the SFRP1 protein, alone or in combination with other strategies, into a hopeful therapeutic target to try to stop the disease in early stages.

“We already know that protein is present in the blood and that its levels increase with aging. We have yet to analyze its predictive value, that is, to see if the blood levels of SRFP1 are elevated early in people who develop the disease, “said Bovolenta.

To reach this conclusion, they used samples of cerebrospinal fluid from patients in early to advanced stages, as well as analysis in postmortem samples of brain tissue. In addition to observations made in humans, they have used mouse models to test their hypotheses.

They checked in rodents that the overexpression of SFRP1 in the brain accelerates the appearance of amyloid plaques, inflammation marks, and alterations in neurons. On the contrary, its inactivation, either genetically or with antibodies that neutralize SFRP1, favors the non-toxic processing of the amyloid precursor protein (APP).

Thus, the neutralization of SFRP1 reduces the accumulation of amyloid plaques in rodents, improves histopathological features related to the disease, and prevents memory loss and cognitive deficits. “These results provide proof of concept that reducing protein levels has a positive effect, at least when applied in the early stages,” he said.