Down syndrome is the most common genetic cause of intellectual disability and is due to the partial or complete presence of an extra chromosome 21 (known as 'trisomy 21'). The current prevalence in the general population is estimated to vary between 1:1,000 and 1:2,000 births. Intellectual disability is constant but of variable degree. In addition, the development of Down syndrome may be affected by premature ageing and the onset of Alzheimer's disease.

The role played by insulin signalling in the brain is well known, and it is particularly crucial to cognitive functions such as memory and learning. Several previous studies showed that alterations in this signal in the brain, known as cerebral insulin resistance, are at the root of cognitive decline both during the normal ageing process and during the development of neurodegenerative diseases such as Alzheimer's, which is characterised by the onset of dementia.

A group of researchers coordinated by Eugenio Barone and Marzia Perluigi of the Department of Biochemical Sciences "A. Rossi Fanelli" at Sapienza University of Rome, in collaboration with the Down Syndrome Centre of Bambino Gesù Children's Hospital - which takes care of about 800 children and young people with Down syndrome and which contributed with its large clinical records to recruit the children involved in the study - and the Policlinico Gemelli Foundation of Rome, have highlighted for the first time that alterations in the insulin signal at brain level occur very early in children and adolescents with Down syndrome. Regardless of trisomy 21, these paediatric alterations have a significant impact on the intellectual disability suffered by children with Down syndrome. Moreover, the Sapienza researchers have highlighted the possibility of identifying this type of alteration using a simple blood sample. The study results were published in the journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association.

"What we think," explains Eugenio Barone of Sapienza University, "is that the persistence of this type of alteration may facilitate the early development of Alzheimer's disease in these people".

"This work represents an important discovery for three main reasons", says Marzia Perluigi of Sapienza University. "First, we proved that these alterations occur very early, even in children with Down syndrome." The second reason concerns the method: being able, with a blood sample, to trace brain alterations that cannot at present be diagnosed in any other way.

"The third reason", Barone concludes, "is that identifying the alterations that occur in the brain as early as possible, especially in children with Down syndrome, will make it possible to study the causes of their intellectual disability even more thoroughly, thus opening the way to potential treatments that will improve their quality of life.

References: 

Aberrant crosstalk between insulin signaling and mTOR in young Down syndrome individuals revealed by neuronal-derived extracellular vesicles - Marzia Perluigi, Federico Marini, Giuseppe Familiari, Emanuele Marzetti, Anna Picca, Elita Montanari, Riccardo Calvani, Roberto Matassa, Antonella Tramutola, Fabio Di Domenico, D. Allan Butterfield, Alberto Villani, Kenneth J. Oh, Emanuele Marzetti, Diletta Valentini, Eugenio Barone - Alzheimer’s & Dementia: The Journal of the Alzheimer's Association DOI: 10.1002/alz.12499

Further Information

Eugenio Barone 
Department of Biochemical Sciences "A. Rossi Fanelli"
eugenio.barone@uniroma1.it

Marzia Perluigi
Department of Biochemical Sciences "A. Rossi Fanelli"
marzia.perluigi@uniroma1.it