A genetic mutation linked to early Alzheimer's in Jalisco
Did you know that in some families in Jalisco a genetic variant has been identified: the Jalisco Mutation, the gene that causes Alzheimer's before the age of 65?
It is known as Jalisco mutation or A431E It has sparked the interest of the scientific community due to its presence in families in the Los Altos region. This alteration is found in the PSEN1 gene and is associated with an inherited form of early-onset Alzheimer's disease, which can manifest around age 40.
Unlike the more common forms of Alzheimer's, which typically appear in old age and are linked to multiple factors, this variant has an autosomal dominant inheritance pattern. This means it can be passed from one generation to the next.
Research on the Jalisco Mutation reminds us of the importance of knowing family history and understanding how genetics can influence certain neurological diseases.
But what does it mean to have a hereditary mutation? How is it transmitted? Is it possible to identify it through genetic testing? And, above all, what options exist for families who wish to investigate a possible genetic predisposition?
What is the Jalisco Mutation and why is it linked to Alzheimer's?
The Jalisco Mutation is the name given to the variant A431E of the PSEN1 (presenilin 1) gene.
This gene is involved in processes related to cell function and protein processing in the brain. Certain pathogenic variants of PSEN1 can cause early-onset familial Alzheimer's disease.
According to research published by the University of Guadalajara Gazette, scientists from the University Center of Los Altos have studied the presence of this variant in families in the Los Altos region of Jalisco.
A scientific study published in 2020 in American Journal of Medical Genetics Part C: Seminars in Medical GeneticsThe study analyzed families in Jalisco with early-onset autosomal dominant Alzheimer's disease. Among the patients evaluated, the researchers reported an average age of symptom onset of 42.5 years.
They also described various clinical manifestations, including language disorders, neuropsychiatric symptoms, and motor problems.
These findings help us understand why the Jalisco Mutation is relevant to medical research and to families with a history of early-onset Alzheimer's.
Alzheimer's in Jalisco: How is the A431E mutation inherited?
One of the most important characteristics of this variant is its autosomal dominant inheritance pattern.
What does this mean?
When a person has an autosomal dominant pathogenic variant, each of their children has a 50% chance of inheriting it. This probability is independent for each pregnancy and applies to both males and females.
This does not mean that everyone with a family history of Alzheimer's carries the Jalisco Mutation. Nor does having a family member diagnosed with Alzheimer's confirm the existence of a specific genetic alteration.
However, certain background factors may justify a specialized assessment:
- Parents, grandparents, siblings or uncles diagnosed with Alzheimer's before the age of 65.
- Several family members from different generations with a history of early-onset dementia.
- Family members who began to show memory problems, language problems, or behavioral changes at unusually young ages.
- Family history of a previously identified genetic variant.
When such a history exists, a neurologist or geneticist can assess whether a genetic study is appropriate.
Can the Jalisco Mutation be detected through a genetic test?
Yes. The A431E variant is located in the PSEN1 gene, so a study that properly analyzes this gene could be a tool to investigate its presence.
Genetic tests currently exist that analyze genes related to hereditary Alzheimer's. One of them is the Invitae Hereditary Alzheimer's Disease Panel, designed to investigate variants in three genes associated with hereditary forms of this disease:
- PSEN1: related to early-onset hereditary Alzheimer's disease.
- PSEN2: associated with another hereditary form of Alzheimer's.
- APP: related to early-onset familial Alzheimer's disease.
The study uses next-generation sequencing (NGS) to analyze the included genes and also contemplates the analysis of deletions and duplications.
This allows for the investigation of different genetic variants that may be related to the development of hereditary Alzheimer's.
One important consideration: Although the panel analyzes PSEN1, the specific coverage and validation of the A431E (c.1292C>A) variant must be confirmed with the laboratory before requesting it for that specific purpose. If a family already knows that one of its members has this variant, the specialist may also consider testing for that familial variant.
Invitae: Genetic study to investigate hereditary Alzheimer's
He Hereditary Alzheimer's Disease Invitae Panel (code 03504) is an alternative for people in whom there is clinical suspicion of hereditary Alzheimer's, especially when there is a family history of early-onset dementia.
Their goal is to identify genetic variants in PSEN1, PSEN2, and APP that may explain a hereditary condition.
How can it help?
- To supplement a medical evaluation: The results can provide information to confirm a clinical suspicion.
- Identify a possible genetic cause: It allows the investigation of variants associated with hereditary Alzheimer's.
- Guiding family members: When a pathogenic variant is identified, it may be relevant to assess the risk to other family members.
- Facilitating genetic counseling: It helps to understand the inheritance pattern and family implications.
This study is not a general screening test for Alzheimer's disease for the entire population. Its use should be individualized and take into account medical history, family history, and genetic counseling.
Furthermore, a positive result should not be interpreted without professional guidance. The classification of variants and their clinical significance are fundamental to understanding what the result represents.
Who should consider genetic testing for Alzheimer's?
Not everyone needs genetic testing. Its use depends on medical history and a specialist's assessment.
Genetic testing may be relevant when:
- There are several family members diagnosed with Alzheimer's or early-onset dementia.
- A family member experienced symptoms before the age of 65, especially if they started around age 40 or 50.
- A genetic variant associated with hereditary Alzheimer's is known within the family.
- A neurologist or geneticist considers that there is a suspicion of hereditary disease.
When possible, it is usually advisable to begin genetic testing with a family member who already has symptoms and a compatible clinical diagnosis. If a pathogenic variant is identified, the specialist can then advise on testing options for other family members.
It is important to remember that a genetic test does not allow for absolutely certain prediction of all aspects of the disease, nor does it replace neurological evaluation.
Knowing your family history is also part of healthcare.
Research on the Jalisco Mutation demonstrates why it is important to pay attention to family history, especially when there are neurological diseases that appear at early ages.
Today, advances in genomic diagnostics allow us to investigate certain hereditary variants and obtain information that may be relevant to patients and their families.
At Zogen, we facilitate access to genetic testing from international laboratories such as Invitae. We guide patients and healthcare professionals on the available options and support the administrative and logistical process, from the initial request to sample collection and shipment to the appropriate laboratory.
If there is a history of early-onset Alzheimer's in your family, consult with a neurologist or geneticist to find out if genetic testing might be appropriate.
Learning more about our genetics can help us better understand our health and make more informed medical decisions.
Bibliographic references
- UDG Gazette. They are tracking the “Jalisco Mutation” in Los Altos: it causes Alzheimer's before the age of 65. University of Guadalajara.
https://www.gaceta.udg.mx/rastrean-en-los-altos-la-mutacion-jalisco-provoca-alzheimer-antes-de-los-65-anos/ - Dumois-Petersen, S. et al. (2020). Autosomal dominant early onset Alzheimer's disease in the Mexican state of Jalisco: High frequency of the mutation PSEN1 c.1292C>A and phenotypic profile of patients. American Journal of Medical Genetics Part C: Seminars in Medical Genetics.
https://doi.org/10.1002/ajmg.c.31865 - Invitae. Hereditary Alzheimer's Disease Panel. Test 03504. Official catalog of genetic tests.
https://www.invitae.com/providers/test-catalog/test-03504 - Labcorp. Invitae Hereditary Alzheimer's Disease Panel. Test 900098. Technical information, genes analyzed and methodology.
https://www.labcorp.com/tests/900098/invitae-hereditary-alzheimer-s-disease-panel
