Although aging is the main risk factor for the development of Alzheimer’s disease, emerging evidence suggests that metabolic disturbances such as type 2 diabetes are also important contributors to its development. In fact, several studies have described a close relationship between Alzheimer’s and diabetes II, with clinical evidence showing that both diseases coexist. However, the mechanisms underlying this relationship were not entirely clear.
Now, a study published in Fluids and Barriers of the CNS in which the researchers from the University of Cádiz Mónica García Alloza and María Vargas Soria participate, together with the professor of the Department of Physiology of the University of Granada Juan José Ramos Rodríguez, has detected that diabetes favors the soluble forms of amyloid beta peptide, which are especially toxic and damaging to neuronal tissue. All of this seems to facilitate the rupture of blood vessels in the brain and enhance neuronal death, typical of Alzheimer’s disease.
The description of the amyloid beta peptide deposition process in the combined model of Alzheimer’s disease and diabetes offers a new therapeutic target on which to work to slow down or prevent the development of this dementia. This is one of the main ways to explore in the future.
Why prediabetes contributes to cognitive decline
In recent years, diabetes and prediabetes have been identified as a risk factor for dementia, but the mechanisms that mediate this relationship are not entirely known. This work sheds light on one of the ways in which type 2 diabetes mellitus or its previous phase, prediabetes, contributes to cognitive decline and accelerates the progress of Alzheimer’s disease. The study describes a new evolution of amyloid beta pathology in Alzheimer’s patients who also suffer from prediabetes or type 2 diabetes.
The novelty of the results obtained is based on the detection of a different progression of the amyloid beta pathology when only Alzheimer’s disease is suffered and another evolution when this dementia is suffered together with type 2 diabetes or prediabetes. In the combined model, a greater accumulation of beta amyloid peptide is observed at the vascular level, which is known as beta-amyloid angiopathy. In addition, diabetes favors the soluble forms of amyloid beta peptide, the most toxic and damaging to neuronal tissue. Said modification of the beta-amyloid pathology increases oxidative stress at the neuronal and vascular level. All this facilitates the rupture of blood vessels in the brain and enhances the neuronal death typical of Alzheimer’s disease.
The research has been developed thanks to a sophisticated multiphoton microscopy technique in live animals, which allows monitoring of the same animal and a brain pathology over time. “This reduces the number of animals needed in the research, without a doubt a great advantage over more rudimentary techniques, which triple the number of animals needed to carry out an equivalent study”, explains UGR professor Juan José Ramos. ‘In vivo’ multiphoton microscopy is a technique within the reach of few laboratories, capable of offering data and images that could not be achieved with other techniques. “The next question we ask ourselves is: by controlling diabetic pathology, can we control or reduce the progression of beta-amyloid pathology and its consequences?” concludes the researcher from the University of Granada.
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