Since Elizabeth Blackburn and Carolyn Widney were awarded the Nobel Prize in Physiology and Medicine in 2009 for their findings on
telomeres and telomerase in relation to cell aging
and longevity, knowledge has grown steadily.
Telomeres are
repetitive sequences located at the ends of the chromosome
and have the function of protecting it and maintaining its stability, while telomerase is an enzyme in cells that helps them stay alive by adding DNA to telomeres.
The length of the ends of the chromosome are considered a
marker of biological age
because there is evidence that longevity is directly related to them and that these, with each cell division throughout the years of life, are getting shorter, which causes their aging.
It is also known that there are factors that influence its shortening, in addition to age, such as tobacco use, a bad diet, exposure to pollutants or stress.
The
relationship between many diseases and accelerated telomere shortening
has been described , such as cardiovascular diseases, diseases of the central nervous system, cancer, diabetes, and even infertility.
Now
two studies
shed new light on the relationship between telomere length and neurodegenerative disorders and the risk of Alzheimer's disease.
The two studies indicate that genetic variants associated with a longer telomere length may be related to a lower risk of developing Alzheimer's.
These genetic variants (many genes are implicated) are related to lower levels of some Alzheimer's biomarkers, such as the
p-tau protein
, as well as greater cortical thickness in cognitively healthy people with a high genetic predisposition to the disease.
The two studies have been carried out at the research center of the Pasqual Maragall Foundation, the Barcelonaeta Brain Research Center (BBRC), and have included participants from
the ALFA Study
, promoted by the "La Caixa" Foundation, a cohort of people without cognitive alterations. but at risk of developing the disease because they are direct descendants of those affected.
The first study, published in the
Computational and Structural Biotechnology Journal
, concludes that genetic variants associated with longer telomeres could have a
protective effect
on the risk of developing Alzheimer's disease and that, in addition, they would be significantly associated with greater Life expectancy.
In the second, published in
Alzheimer's Research & Therapy
and with the collaboration of the research team from the Bellvitge Hospital Biomedical Research Institute (Idibell), this possible relationship has been analyzed through
brain, cognitive and liquid biomarkers. Cerebrospinal
disorders of Alzheimer's disease and neurodegeneration.
For this study, samples from participants in the ALFA Study have been used, a cohort that includes a population of cognitively healthy individuals at risk of suffering from Alzheimer's.
significant associations
The main results of this research reveal significant associations between genetic variants that predict longer telomere length and lower levels of some Alzheimer's biomarkers, such as the p-tau protein.
In addition,
inheriting longer telomeres
has been linked to increased cortical thickness among people with a high genetic predisposition to future Alzheimer's disease.
The continuity of these studies is important in order to understand the role of telomere length in the development of Alzheimer's disease.
According to Marta Crous-Bou, a BBRC collaborating researcher and co-leader of the project, although the findings are positive, "they
need to be replicated in larger cohorts
, including participants at different stages of disease development, as well as follow-up of participants of the ALFA study and additional observational analyzes to better understand the results obtained and underlying biological mechanisms".
Natàlia Vilor-Tejedor, co-senior investigator of the study and leader of the BBRC Neurobiogenetics team, specifies, for her part, that "genetic variants associated with greater telomere length could protect brain structure
through multiple mechanisms
, either in regions affected mainly by processes related to Alzheimer's or aging itself".
When asked by this newspaper, Vilor-Tejedor reports that the importance of these two works resides in the fact that they relate the length of telomeres to Alzheimer's and that the association of these repetitive sequences located at the ends of the chromosome with neurodegeneration is something
very little studied
.
Another detail that makes them relevant is that the sample is not sick but healthy people, relatives of sick people or with genetic risk factors included in the
ALFA Study
, which is a research platform to identify the early pathophysiological characteristics of Alzheimer's disease, as well as as its early detection, and to be able to develop prevention strategies.
It was launched in 2013.
Specific common and rare variants
It so happens that this month, two new rare genetic variants have joined the three already known and the
75
previously described common ones in relation to the risk of developing Alzheimer's disease thanks to an international study published in
Nature Genetics
and developed with the participation of the Dementia Neurobiology Group and the Memory Unit of the Sant Pau Hospital Research Institute (IIB Sant Pau).
Now the
rare variants
They are in five genes: the already known SORL1, ABCA7 and TREM2 and the new ATP8B4 and ABCA1.
Vilor-Tejedor has pointed out that they hope, for their part, to soon be able to publish new evidence on genetic variants in people with risk factors but who have not developed the disease.
Regarding the possibility of having a risk test that takes into account both genetic variability factors and telomere length, he has indicated that it would also have to take
non-genetic factors
into account since genetics explain little of the development of the illness;
only 1% of cases show a causal relationship.
And he remembers that telomere length is also related to environmental factors.
Vilor-Tejedor recalls that the length of telomeres is also related to environmental factorsBBRC
The expert is confident, however, that despite the complexity of establishing the real individual risk, progress can be made towards personalized preventive measures in Alzheimer's, which is, after all, what it is about (the objective).
Correlation with significant changes?
The BBRC announced in 2019 that it was beginning a study to determine whether telomere length correlates with cognitive changes and changes in brain structure and functionality in the
preclinical phase
of Alzheimer's, a work for which Crous-Bou is the principal investigator.
Once the telomeres have been measured, the researchers assess whether their length is associated with cognitive performance, as evidenced in memory tests.
"Since we follow these people, our working hypothesis is that those who
lose memory the fastest
may be those who initially have shorter telomeres," Crous-Bou said at the time.
A parallel is also drawn between the length of the telomeres and the structure and functionality of brain areas related to the disease -through
MRI images-
, as well as with the presence in CSF and blood samples of neurodegeneration biomarkers involved, such as the peptide beta-amyloid, tau protein and neurofilaments.
Vilor-Teledor indicates about this other study that is parallel and that they hope to be able to publish their results soon.
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