An international team has discovered a new genetic mutation related to early-onset Alzheimer’s disease in several members of a single family residing in Sweden. This is the first time that a deletion (elimination) of multiple amino acids of the amyloid protein (APP) has been identified that leads to the early onset of Alzheimer’s, explains to ABC Salud the Spanish researcher María Pagnon de la Vega, first author of the study published in the magazine «
Science Translational Medicine».
Call ‘deletion of APP Uppsala‘, because the three identified members of that family are from that Swedish locality, it is the first family that specifically has this deletion of six amino acids and Pagnon of
La Vega and his colleagues define this form of Alzheimer’s disease as “autosomal dominant,” that is, it passes from one generation to the next and progresses rapidly.
The best-known case of familial Alzheimer’s is one of the 25 families in an area of Colombia that have a mutation in the gene for presinilina 1 -located on chromosome 14- which causes a change from glutamic to alanine. This alteration in amino acids generates the appearance of protein waste known as amyloid.
The researchers explain in their work there is no data to suggest that other families carry the APP deletion of Uppsala, although other forms of familial Alzheimer’s have been identified in Sweden.
In the case of the carriers, they write, they all had a deletion in a specific chain of amino acids that are part of the amyloid precursor protein. Amino acids are missing.
Imagine a much shorter pearl necklace, resulting from the absence of six beads, the researchers explain in their study.
The amino acid beads are not on the strand because the APP gene of this Swedish family does not encode them. In terms of numbers, the deletion cuts a six amino acid strip, causing damaging deposits of Aβ protein throughout the brain.
Most Alzheimer’s cases arise sporadically, after the age of 65.
However, in addition to Alzheimer’s dementia that begins sporadically in old age, there are familiar forms that begin years or decades earlier.
Now this international team of scientists, led by neurobiologists in Sweden, has identified an extraordinarily rare form of the disease that has so far only been found in one family.
This new form of Alzheimer’s is aggressive, fast and ‘steals’ the most productive years of its victims throughout their cognitive functions.
“The affected people have an age of onset of symptoms of around 40 years and suffer a course of the disease that progresses rapidly”, explains the Spanish researcher.
Together with his colleagues from the Department of Public Health and Healthcare Sciences
Uppsala University (Sweden), Pagnon de la Vega collaborated with a large team of neuroscientists, structural and molecular biologists, and imaging experts across Europe.
The researchers thus found that the mutation accelerates the formation of protein plaques that damage the brain, known as beta amyloid, or more simply as Aβ. The plaques destroy neurons and, as a result, wipe out the executive functions of the brain itself.
Executive functions are working memory, mental flexibility, and self-control.
Scientists believe that the consequences of this deletion make the disease more aggressive because large amount of beta-amyloid protein is produced due to the mutation.
Other forms of Alzheimer’s have been linked to mutations in the APP gene, but this is a deletion that Pagnon de la Vega and his colleagues confirmed in about 500 samples through genetic analysis, structural biological research, amino acid and protein chemistry studies, and spectrometry. mass to characterize amyloid. —The deleterious protein — that permeates the brain tissue of mutation carriers.
The family history behind this genetic discovery began seven years ago in Sweden when two brothers attended a memory disorder clinic in the
Uppsala University Hospital, where they were evaluated for their memory problems, loss of orientation and mental acuity. At just 40 and 43, sadly, the siblings weren’t the only ones whose minds were confused and unraveled. Another relative his own age was experiencing nearly identical symptoms.
His cousin went with the siblings to the same memory disorders clinic to evaluate the cognitive problems that were affecting their memory, causing them to be unable to express themselves with clear and reflective sentences, and disabling their ability to perform simple mathematical operations.
All three were diagnosed with early-onset Alzheimer’s. However, they weren’t the only ones within this family.
Two decades earlier, doctors had treated the father of the two brothers. He was also in his early 40s when the symptoms first appeared. The health workers evaluated the father at the same memory disorders clinic where his children had become patients with Alzheimer’s.
By the time the two brothers and the cousin arrived at the memory disorder clinic, they were all showing severe symptoms. They had trouble speaking and had lost their ability to perform simple math.
The scientists also determined that they had difficulties with executive functions, and brain scans revealed the characteristics of Alzheimer’s in all three. Brain scans revealed evidence of atrophy in the frontoparietal and mediotemporal regions of the brain.
In addition, the valuation by means of the Mini Mental State Exam, an assessment that the elderly are frequently used to assess cognitive abilities, showed that their score was only low, but was in a range generally seen in older adults with cognitive impairment. They were all in their 40s at the time of the test.
«Symptoms and biomarkers are typical of Alzheimer’s disease, with the exception of normal cerebrospinal fluid», Details Pagnon de la Vega.
Before the discovery of the deletion, more than 50 APP gene mutations had been identified worldwide and are associated with the early onset of Alzheimer’s disease.
APP mutations, in general, are responsible for less than 10% of all early-onset cases.
Unless a cure is found, the disorder is expected to overwhelm global healthcare systems by 2050 due to the inexorable aging of the population, according to the World Health Organization.
But, María Pagnon concludes, research like ours is a learning process that allows us to continue investigating to better understand the disease. “We still don’t know what target we have to target.”
George is Digismak’s reported cum editor with 13 years of experience in Journalism