Can Alzheimer’s Be Inherited

Ethics Approval And Consent To Participate

The study was approved by the Medical Ethical Committee of the Erasmus Medical Center Rotterdam. Brain autopsy was conducted by the Netherlands Brain Bank at the designated premises of the VU Medical Center in Amsterdam . Ethical approval for the NBB procedures and forms was given by the Medical Ethics Committee of the VU Medical Center. Written informed consent for the use of tissues, clinical, and neuropathological data was obtained from all participants or their legal representatives, according to the Code of conduct for Brain Banking and Declaration of Helsinki.

Genetic And Hereditary Risk Factors For Alzheimer’s Disease

• Genetic Testing

As the incidence of Alzheimers disease continues to rise, so too does the push for medical science to discover the cause of the disease. Is it genetic? If so, what are the hereditary risk factors of Alzheimers disease?

This article looks at the genetic and hereditary risk factors of Alzheimers disease and how genes influence late- and early-onset Alzheimer’s.

ThomasBarwick / Getty Images

Is Alzheimers Inherited Scientists Say Alzheimers Not Inherited In 99% Of Cases

It is important to note that in the 99% of cases, Alzheimers is not inherited. Having a certain set of genes can increase the risk of Alzheimers in the remaining one percent. Under one theory, it can be inherited through the maternal line. Some scientists, such as Dr. Lisa Marconi, say persons whose mothers had Alzheimers with a high level of amyloid protein have a greater risk of being affected compared to others with a paternal instance of Alzheimers or with families with no Alzheimers history. The small number of inherited cases, however, usually appear in early onset than those who show no signs of inherited Alzheimers. The age range for early onset Alzheimers is between 30 and 60 years old.

The only certain thing about the risk of Alzheimers is that age is the single most important risk factor. The most common gene associated with Alzheimers disease in elder persons is called apolipoprotein E . studies show this gene:* APOE E2 seems to reduce the risk,* APOE E4 seems to increase the possibility of Alzheimers disease,* E3 seems to have no effect at all.

All persons take one gene from their mother and another from their father. If a person has two copies of APOE E4, the possibility of developing Alzheimers is greater than if two copies of APOE E2 are inherited. It is important that even in this case, it is not certain that persons with two copies of APOE E4 exhibit Alzheimers and people with two copies of APOE E2 do not.

You May Like: Can Alzheimer’s Happen At Any Age

Why I Dont Want To Know My Genetic Risk For Alzheimers Disease

I have studied brain health and risk reduction for Alzheimers disease and related dementias for more than ten years. While there is no disease-modifying therapy available on the market today, there is emerging evidence that many common-sense lifestyle choices can improve the resilience of our brains and decrease our risk of developing dementia.

In 2017, the Lancet Commission released a growing body of evidence suggesting that nine risk factors could be modified to help delay or prevent dementia: less education, hypertension, hearing impairment, smoking, obesity, depression, physical inactivity, diabetes and low social engagement. In 2020, the Commission added three more modifiable risk factors to its list to make a total of twelve, accounting for around 40 percent of worldwide dementias.

My father and his three siblings all had late-onset Alzheimers disease. It is a cruel, mind-robbing disease, and I wish it upon no one. This is why in 2020 I launched the Milken Institute Alliance to Improve Dementia Care, a cross-sector collaborative that includes more than 60 leaders across eight stakeholder groups: advocacy, research, health systems, industry, philanthropy, government, community-based organizations and people living with dementia and their caregivers.

Im not sure what I would do differently if I knew I had the APOE e4 gene, so I choose not to be tested.

Reducing Risk Already

Why I Want To Know My Genetic Risk For Alzheimers

Genes are one of many risk factors for Alzheimers and related dementias. Science is evolving on the influence of alleles such APOE e4, the most common variant associated with Alzheimers disease, across age, gender, race and ethnicity. To date, routine genetic testing in medical care is not widely recommended. It is estimated, however, that more than 100 million people have undergone direct-to-consumer genetic testing, and this market is expected to grow.

UsAgainstAlzheimers does not hold a position on consumer genetic testing and recommends consulting with a healthcare provider about brain heath and considering genetic counseling in concert with any DNA test. To learn more about the genetics of Alzheimer’s disease and the contribution of the APOE genes, check out the National Institute on Aging’s Alzheimer’s Disease Genetics Fact Sheet.

I used the direct-to-consumer DNA test 23andMe to learn I have one copy of the APOE e4 gene, the most common genetic variant associated with Alzheimers disease. This increases my lifetime risk of developing Alzheimer’s disease by a little more than two times, on average. About 10 percent to 15 percent of people carry one copy of APOE4 and 2 percent to 3 percent carry two copies.

But what happens when the impediment cannot be moved? Like many people, I thought that my genes were outsized determinates of my fate and I did not want to look into the genetic crystal ball at something I could not control.

Not Powerless

Read Also: Does Early Onset Alzheimer’s Progress Faster

What To Do If Someone In Your Family Is Diagnosed With Alzheimer’s

• Contact the Alzheimer’s Association . Find out about resources available to help you and your family. State and county agencies may also be able to help.

• Plan for the future. This includes legally designating someone to make health care and financial decisions for the affected person when he or she can’t.

• Investigate long-term care options. Nursing care is expensive, and finding a good place can take time. Start early.

• Take care of physical health. People with dementia who live a healthy lifestyle tend to progress more slowly to the later stages.

• Steer away from genetic testing. Even if you have the APOE Alzheimer’s risk gene, it usually doesn’t mean you will develop dementia later in life.

Image: Thinkstock

Dementia Affects The Person Diagnosed But Also Raises Fears For Siblings And Children Here Are The Facts

After a diagnosis of Alzheimer’s disease, families face fears and difficult medical decisions.

Alzheimer’s disease represents a personal health crisis, but it’s also a family concern. What does it mean for your children or siblings if you are diagnosed with Alzheimer’s? What does it mean for you if a close relative develops the condition?

“People think that if their dad or aunt or uncle had Alzheimer’s disease, they are doomed. But, no, that’s not true,” says Dr. Gad Marshall, assistant professor of neurology at Harvard Medical School. “Even though family history adds to the overall risk, age still usually trumps it quite a bit. It means your risk is higher, but it’s not that much higher, if you consider the absolute numbers.”

Also Check: Does Tinnitus Lead To Dementia

Replication Of Candidate Variants

To replicate the association of our candidate variants with AD, we used exome sequencing data available from Dutch studies contributing to the Alzheimer Disease European Sequencing consortium and from the Amsterdam Human Genetics department consisting of 833 EOAD patients, 521 LOAD patients, and 6949 healthy controls. The set of samples was pruned such that no family relations remained. Only variants with a MAF < 0.1% were selected and results were categorized based on CADD score . Population structure was corrected for with 10 PCA components. Only genes with 10 carriers were considered for subsequent analysis. Quality control and burden tests were performed using ordinal logistic regression with an EOAD > LOAD > controls labeling as recently described . This method exploits the assumption that the genetic risk will be enriched towards EOAD patients, as can be expected for the candidate variants and genes in this study. Variant-specific analyses were performed with the same approach . P-values were adjusted for multiple testing using the FDR approach , with FDR < 0.05 considered as suggestively associated with AD.

Functional Interpretation Of Gwas Signals And Gene Prioritization

To prioritize candidate genes in the new loci, we systematically searched for evidence for these genes in seven different domains: variant annotation, eQTL-GWAS integration, sQTL-GWAS integration, protein QTL -GWAS integration, mQTL-GWAS integration, histone acetylation QTL -GWAS integration and APP metabolism. On the basis of this evidence, we then defined a gene prioritization score of between 0 and 100 for each candidate gene . Detailed information on the domains, categories and subcategories is given in Supplementary Table . A brief summary of how evidence was assessed in each domain is provided below, together with a detailed description of the gene prioritization strategy.

Candidate genes

We considered protein-coding candidate genes within a ±1-Mb window of the new lead variants. The genes in overlapping loci were assigned to their respective loci based on proximity to the lead variants, and the distal genes were not considered for gene prioritization in the investigated loci. Moreover, we did not perform gene prioritization in the complex IGH gene cluster locus , as this telomeric region contains complex splicing events that probably result from known fusion events.

The variant annotation domain

In this domain, we determined whether the candidate gene was the nearest protein-coding gene to the lead variant and/or whether the lead variant was a rare variant and/or protein-altering variant of the investigated candidate gene.

Molecular QTLGWAS integration domains

Recommended Reading: What Are The Stages Of Frontotemporal Dementia

Can Vascular Dementia Be Inherited

In most cases, vascular dementia itself is not inherited. However, the underlying health issues that sometimes contribute to this condition, such as high blood pressure or diabetes, may be passed on from one generation to another.

Other than in a few, very rare cases, parents cannot pass on vascular dementia to their children. However, a parent may pass certain genes that increase the risk of developing vascular dementia.

The sort of genes that increase the risk of vascular dementia are often the same ones that increase the risk of high blood pressure, diabetes, heart disease and stroke.

For this reason, having a healthy lifestyle, such as eating well and staying physically active, are probably more important for preventing vascular dementia than they are in Alzheimer’s disease.

Dementia And Down Syndrome

People with Down syndrome are born with an extra piece of DNA. This means they also have an extra copy of the APP gene. This leads to the build-up of amyloid plaques in the brain, which play a role in the development of Alzheimers disease. While not everyone with Down syndrome will go on to develop symptoms of Alzheimers, most people with the condition over the age of 40 will have amyloid build-up. It is estimated that about 50% of people with Down syndrome develop symptoms like memory loss, usually in their 50s and 60s.

To find out more about Down syndrome and dementia you can contact Downs Syndrome Association helpline on 0333 1212 300 or visit their website www.downs-syndrome.org.uk.

Recommended Reading: Why Do Dementia Patients Get So Angry

Genetic Data Generation And Processing

For the majority of patients, single nucleotide polymorphism arrays were available as part of the European Alzheimers and Dementia Biobank . Details on data generation and processing have been described previously . Exome sequencing data were generated for all selected patients and eight unaffected relatives. Genomic DNA was extracted from whole blood or frozen post-mortem brain tissue using standard laboratory procedures. DNA samples were paired-end sequenced using Illumina sequencers, after capturing using either Nimblegen SeqCap EZ v3 or v2 capture kits. Raw sequencing data from all sites were collected on a single site and processed using a uniform pipeline as reported recently . In brief, sequenced reads were processed using the Burrows-Wheeler Aligner Tool, Picard, and Samtools, and GATK was used for variant calling and quality control according to best practices . All samples were jointly genotyped into a single dataset VCF file . Subsequently, a family-VCF was generated for each family. Population database frequencies and functional and impact scores were annotated to variants using ANNOVAR .

Genes Those Little Unknowns

The scientific definition of a gene1 would be a short segment of DNA translated into protein. Another definition would also be the transmissible unit of biological inheritance. Thus, if a gene is a short segment of DNA, we call the genome the total sequence of DNA that a living being, or a particular species possesses. But in a more educational or metaphorical way, we could say that genes are the characters in our story.

DNA is a nucleic acid that contains the genetic instructions used in the development and functioning of living organisms.

Its main function is the storage of information to build cells, proteins and other molecules. In each human cell we have more than 22,000 genes grouped in 23 pairs of chromosomes with the necessary information for our growth, development and functioning. 2,3.

In addition, DNA is responsible for hereditary transmission, that is, for the genetic information that is passed from parents to children. But how is this genetic information carried from generation to generation?

We all have two copies of each of our genes, one we inherit from our mother and one from our father. An allele is each different version of a gene. For example, the ABO gene4 codes for the human blood group protein ABO, which has at least three alleles: A, B and O.

The combination of genes that we have inherited is called the genotype, while the phenotype is the result of how our body reflects being a carrier of these genes in interaction with the environment.

You May Like: When Does Alzheimer’s Start Age

Evaluating The Risk Imposed By Apoe And Rare Vus

We identified a substantial burden of APOE, with heterozygous 4-allele carriers in 67% of the families and homozygosity in 50%. Although the risk conferred by two APOE-4 alleles can cause semi-dominant inheritance with AD lifetime risk estimates of 30% by 75 years of age , we cannot be sure if APOE might be the sole genetic factor in these families, or whether some carry additional factors genetic and/or environmental to trigger disease initiation.

Following the relatively low burden of APOE and PRS in families with a known pathogenic variant, we anticipated a similar low burden in families with a VUS, if these are pathogenic. However, six out of eight families with a VUS showed a high occurrence of APOE-4 homozygosity. Moreover, we did not observe a difference in PRS across families with and without a VUS. It suggests that the identified VUS are insufficient by themselves to cause disease and that the genetic burden for AD in these families is multifactorial, although individual families might have a high burden of APOE or PRS by chance, on top of a monogenic cause.

Which Genes Are Responsible For Alzheimers

APOE-e4 is the most common gene associated with Alzheimers, but it is only a risk gene. It doesnt necessarily guarantee youll develop the disease.

Alzheimers disease genetics can seem complicated. That might be because researchers dont know every gene on every chromosome that may lead to Alzheimers. But scientists have figured out 3 deterministic genes that result in Alzheimers disease, as well as several genes and genetic mutations that bring a greater risk of Alzheimers.

Deterministic genes are only found in an estimated 1% of Alzheimers cases. Here are the 3 deterministic genes that directly cause Alzheimers, particularly early-onset Alzheimers disease:

Mutations or variations of the following genes may put you at higher risk of Alzheimers, especially late-onset Alzheimers disease:

Apolipoprotein E-e4 was identified in 1993 as the first gene variation found to increase the risk of Alzheimers disease. According to the Alzheimers Association, researchers estimate that between 40-65% of people diagnosed with Alzheimers have the APOE-e4 gene.

There is a blood test that tests for APOE-e4. This genetic test helps inform an Alzheimers diagnosis, though it cannot diagnose Alzheimers by itself.

Read Also: What Are The Beginning Signs Of Dementia

Is Dementia Passed On Through Our Dna

Medical research seems to suggest that it is very unlikely that dementia can be passed on through our DNA. But in rare cases, some diseases that lead to dementia can be passed on through our DNA. But it is still extremly rare that if a family member such as a parent or grandparent has developed one of the many different kinds of dementia, that their children will inherit the disease at some stage in their life.

This is not to say that somebody with Alzheimers cannot have not passed on the disease from parent to child. It is possible they could have. In some rare cases of Alzheimers, the disease can be inherited from a parent. But this is very rare.There is a group of four genes a person can carry that can lead to a greater risk of Alzheimers. With 3 of the four genes being responsible for early onset dementia in people in their 30s, 40s and 50s with the other gene being responsible for Alzheimers in older people, usually over 65 years of age.

In the majority of cases of Alzheimers the disease is mostly associated with old age. Most cases are diagnosed with people in their 70s and 80s which is often referred to as Senile dementia.

How Genetics Impact Your Risk Of Alzheimers

There are certain genes/mutations that increase your risk of Alzheimers, and a few very rare genes/mutations that may directly cause Alzheimers disease.

These extremely rare genes that directly cause Alzheimers are called deterministic genes. Those that only increase your chances of developing Alzheimers are called risk genes.

Experts do not recommend routine genetic testing to diagnose Alzheimers. There may be very rare genes that may directly cause early-onset Alzheimers, but genetic testing cannot give you a 100% accurate diagnosis or prediction.

The most common gene associated with higher disease risk is the APOE-e4 allele. Interestingly, individuals with APOE-e2 variation have a risk for the development of Alzheimers.

Does Alzheimers run in the family? Alzheimers runs in the family, in a sense. Those who have a first-degree relative with the disease are at increased risk of developing Alzheimers. This does not equate to a 100% guarantee that youll develop the disease. But genetics seem to partially contribute to developing Alzheimers.

Can you get Alzheimers if it doesnt run in your family? You can get Alzheimers if it doesnt run in your family. The causes of Alzheimers disease are not purely genetic. Age is the biggest risk factor for developing the disease. Everyone older than 65 years old is at risk of developing Alzheimers. However, having no family history of dementia may decrease your risk of dementia.

You May Like: What Is The Definition Of Vascular Dementia