Is Alzheimers Genetic?

Is alzheimers genetic?

Check out this answer from Consensus:

Alzheimer’s disease has a strong genetic component, with both early-onset and late-onset forms influenced by genetic factors. While significant progress has been made in identifying key genes and loci associated with Alzheimer’s, much remains to be discovered. Continued research in this area holds promise for developing targeted therapies and improving outcomes for individuals at risk of this debilitating disease.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia, particularly affecting the elderly. The genetic basis of Alzheimer’s has been a significant focus of research, aiming to uncover the hereditary factors contributing to the disease. This article explores the genetic underpinnings of Alzheimer’s disease, highlighting key findings from recent studies.

Early Discoveries in Alzheimer’s Genetics

The initial breakthroughs in Alzheimer’s genetics occurred in the 1990s with the identification of three genes associated with early-onset familial Alzheimer’s disease (EOFAD): amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2)1 2. These genes are known to cause autosomal dominant forms of the disease, typically manifesting before the age of 65.

The Role of APOE

For late-onset Alzheimer’s disease (LOAD), which is more common and occurs after the age of 65, the apolipoprotein E (APOE) gene has been identified as a major genetic risk factor. The ε4 allele of APOE significantly increases the risk of developing Alzheimer’s, although it does not guarantee the disease will occur1 2 3 4.

Recent Advances and New Genetic Loci

Despite these early successes, much of the genetic risk for Alzheimer’s remains unexplained. Recent genome-wide association studies (GWAS) and meta-analyses have identified additional genetic loci associated with Alzheimer’s. For instance, a large meta-analysis identified 11 new susceptibility loci for LOAD, adding to the growing list of genetic factors involved in the disease3. Other studies have confirmed the involvement of genes such as CLU, CR1, PICALM, and BIN1, which are implicated in various neuropathological processes related to Alzheimer’s4 5 6.

Genetic Complexity and Heritability

Alzheimer’s disease is highly heritable, with genetic factors accounting for an estimated 60-80% of the attributable risk5 7. However, the genetic architecture of Alzheimer’s is complex, involving both common and rare variants. For example, rare variants in genes like TREM2 and UNC5C have been shown to affect Alzheimer’s risk, although they are less common in the population8 9.

Pathophysiological Insights

The genetic discoveries have provided significant insights into the pathophysiology of Alzheimer’s. For instance, the amyloid cascade hypothesis, which posits that the accumulation of amyloid-beta (Aβ) peptides in the brain is a primary driver of Alzheimer’s, is supported by the genetic findings related to APP, PSEN1, and PSEN25. Additionally, the role of microglia, the brain’s resident immune cells, has been highlighted by genetic studies, suggesting that immune response and inflammation are critical components of Alzheimer’s pathology10.

Future Directions

The field of Alzheimer’s genetics is rapidly evolving, with ongoing efforts to identify new genetic risk factors and understand their biological implications. Advances in next-generation sequencing and collaborative research initiatives are expected to uncover additional genetic contributors to Alzheimer’s, paving the way for personalized treatment and prevention strategies2 7 10.

 

 

Is alzheimers genetic?

Erin L Abner has answered Near Certain

An expert from University of Kentucky in Alzheimer’s Disease, Epidemiology

There are two forms of Alzheimer disease (AD): early onset, also known as familial AD, and late onset, also known as sporadic AD. Onset before age 65 is generally considered early onset. The familial form of the disease accounts for about 3-5% of all AD cases, and it is entirely genetic. Mutations in the APP, PSEN1, and PSEN2 genes can all cause familial AD, and onset of symptoms can occur in early midlife. Sporadic AD, which accounts for over 95% of cases, is strongly linked to the APOE gene, specifically the epsilon 4 allele. People with either one or two copies of the APOE4 allele are between 4 and 12 times more likely to develop dementia due to AD compared to people without a 4 allele. There are also many other genes (around 20) that have been linked to sporadic AD, but their individual effects are not nearly as strong as APOE. Overall, we estimate that about 70% of a person’s risk for sporadic AD is explained by genetics.

 

Is alzheimers genetic?

Margaret Gatz has answered Near Certain

An expert from University of Southern California in Psychology

It is almost certain that genetic influences contribute to risk for developing Alzheimer’s disease, but it is also near certain that environmental factors contribute to risk. There are two sources of evidence about genetic influences. One is twin and family studies. Research has shown that people with a first-degree relative with Alzheimer’s disease have approximately double the lifetime risk to develop the disease themselves, compared to those who do not have an affected first-degree relative. Twin studies look at chance of developing a disease if one’s twin has the disease. In identical twins, this concordance rate is upwards of 50%. Concordance for fraternal twins, who are as alike genetically as regular siblings, is nearly half the concordance of identical twins, similar to risk for any first-degree relative. The other source of evidence about genetic influences are studies of genes themselves. There are a large number of genes that each contribute a small amount to increasing risk for Alzheimer’s disease. In particular, for those who carry a certain variant of the Apolipoprotein E gene, risk of Alzheimer’s disease is close to four times greater, compared to those who do not carry this gene. This is all about changes in risk. There are only very, very rare mutations where inheriting the gene almost certainly means that one will develop Alzheimer’s disease. The importance of environmental factors and healthy habits to increasing or decreasing risk for developing Alzheimer’s disease is therefore evident. Some studies compare the environments and health behaviors of those with versus those without Alzheimer’s disease. Other studies evaluate interventions that aim to reduce risk by increasing beneficial health behaviors and protective environments. These studies suggest, for example, that risk for developing Alzheimer’s disease is greater in those who do not engage in physical activity; in those with uncontrolled high blood pressure, diabetes, or obesity in midlife; and possibly among those exposed to greater air pollution. These are all potentially modifiable influences.

 

Is alzheimers genetic?

Eric M Blalock has answered Unlikely

An expert from University of Kentucky in Neuroscience

I am interpreting the question as asking if AD is ’caused’ by genetics. Based on this interpretation I rate it as unlikely because there is a > 95% chance that a given individual randomly selected from the population and diagnosed with Alzheimer’s disease will have the more common sporadic form of the disease rather than the less common familial form of the disease.

There are two forms of Alzheimer’s disease (AD)- familial and sporadic. Familial AD (fAD) is definitely genetic, people that are unlucky enough to inherit the mutated gene structure from the parent with that gene will certainly go on to get fAD if they live long enough. However, fAD represents a pretty small proportion (< 5%) of the total number of AD cases in the world. The vast majority of AD cases (> 95%) are sporadic AD (sAD).

In sAD, there are risk factors that can increase the likelihood of getting the disease. For instance, getting concussions when you are younger, or developing type II diabetes as you age, both increase the risk of getting sAD. However, increasing the risk of something is not the same thing as causing it. We would not say that AD is caused by concussions, or caused by type II diabetes, even though they increase the risk- because many people get these conditions but do not get sAD.

Similarly, there are genetic variants (the most famous is the e4 variant of the APOE gene). If you have a double dose of e4, it increases your risk of getting sAD (but it’s still not certain that you will get sAD). Casting a little wider, being female may or may not increase your risk of getting sAD, but, if you are female, and you do get sAD, you are much more likely to have an aggressive and rapidly progressing presentation of sAD, and, I guess, one could consider being male or female to be genetic in some sense. Casting the net even wider, only humans get sAD or fAD, so in that sense, you do have to have our genes to get the disease- but again, some of us don’t get the disease- so chalk it up to ‘necessary but not sufficient’. But by far, among humans, the single largest risk factor for sAD is aging.

The older term for sporadic AD was ‘idiopathic’- with the same root word as ‘idiot’- meaning it’s bad (pathic) and we don’t know why (idio). We’ve come a long way in figuring how certain genetic changes can alter risk, and in defining the molecular pathways through which these genetic changes may exert their effects- but we know less about how diet, metabolism, life history, aging processes, medication history, psychosocial stress, and a host of other factors might contribute. To over-simplify, asking if age-related sAD is caused by genes or by environment is like asking which edge of the scissors cuts the paper.

 

Is alzheimers genetic?

Daniel  Blazer has answered Likely

An expert from Duke University in Epidemiology, Mental Health, Psychiatry, Neuroscience

The short answer is that yes, in part. Genetics plays a clear role in many cases of Alzheimers disease. Yet there do arise “spontaneous” cases, that is cases in which a person develops Alzheimers without any family history. In addition, more than one gene has been implicated. The genetic contribution to Alzheimers disease is complex. 

 

Is alzheimers genetic?

Steven  Estus has answered Likely

An expert from University of Kentucky in Alzheimer’s Disease, Genetics

Early onset Alzheimers disease (AD), which begins before the age of 65 years, has a very strong genetic component. The impact of genetics is somewhat lower for AD that begins after 65 years of age. Several groups have recently investigated whether AD could be predicted based on an aggregation of AD genetic risk factors (examples in links below). Overall, these results support the idea that genetics contributes the majority of AD risk.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006219/?report=reader and herehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599118/

 

Is alzheimers genetic?

Rafael Franco has answered Extremely Unlikely

An expert from Universitat de Barcelona in Parkinson’s Disease, Alzheimer’s Disease, Antioxidants, Nutrition, Pharmacology, Asthma, Cell Biology, Biochemistry

Only a few percentage of cases are due to mutations (estimated 10-15%)

The rest are known as “sporadic” and not due to genetic issues.

One may always consider that everything depends on your genes, but for sure sporadic Alzheimer’s is not considered to be caused by a specific or a couple of speific mutations in one or two genes.

 

Is alzheimers genetic?

Robert P Erickson has answered Likely

An expert from University of Arizona in Genetics, Neurodegenerative Disease

As Dr. Abner has pointed out, there are strong genetic influences but environmental factors also play a large role–cholesterol levels (although they, too, are influenced by genetics), mental, social, and physical activity levels–and, of course, other factors to be discovered also play a big part. I would lower the genetic component to more like 50 % but readily acknowledge it could be higher or lower.

 

Is alzheimers genetic?

Ali Torkamani has answered Near Certain

An expert from The Scripps Research Institute in Genetics, Bioinformatics, Genomics

These options are incorrect. Alzheimer’s disease has a significant genetic component but is not completely determined by genetics. High end estimate is 80% genetic.

https://www.nature.com/articles/gim2015117

 

Is alzheimers genetic?

Cláudia Guimas Almeida has answered Near Certain

An expert from CEDOC – NOVA Medical School in Alzheimer’s Disease, Cell Biology

The answer to such question is not only yes or no, black or white. Alzheimer’s is far more complex than what we can understand so far and, yes, some determinants that lead to the the disease can be genetic. But Alzheimer’s is a multi-factorial, complex and puzzling disorder, associated with aging and the exact causes that lead to the disease are still unknown. Some forms of Alzheimer’s disease are diagnosed before the age of 65, named as early-onset Alzheimer’s disease, accounting for only 5% of all Alzheimer’s cases. The most common forms of the disease (late onset Alzheimer’s disease) appear later in time but little is still understood about how it starts. Due to this uncertainty, over the past decade, scientists have made an huge effort to understand if some genetic alterations in patients can be in the basis of the disease. For that, genome wide association studies have been performed (and are still being done) and more than 20 independent loci associated with the disease (in addition to APOE) have already been identified. Are they sufficient to trigger the disease or do they have a role to potentiate disease progression? That is a question that remains open.

 

Is alzheimers genetic?

Waqar Ahmad has answered Unlikely

An expert from University of Queensland in Alzheimer’s Disease

I think it is metabolic disease

 

Is alzheimers genetic?

Auriel A Willette has answered Likely

An expert from Iowa State University in Alzheimer’s Disease, Neuroimaging, Genetics, Immunology, Endocrinology

First, my opinion is specific to late-onset Alzheimer’s disease (AD), which is diagnosed roughly after age 65 and makes up 95-99% of AD cases.

AD is not exclusively caused by uncommon variants in genes, but it is thought that these genes play a critical role in the development of roughly 2/3’s of AD cases.

Uncommon variants in some genes appear to be much more important than others. For example, Apolipoprotein E (APOE), originally characterized as a cholesterol transport gene, has the strongest genetic influence by far on AD risk.

One critical factor to consider is that our environment–diet, exercise, socioeconomic status–can dampen or augment how these genes affect AD risk. We know very little about these so called gene-environment interactions. Knowing more about these interactions would help us better understand which genes are most important for AD and under what environmental conditions.

 

Is alzheimers genetic?

Stacey S Cherny has answered Near Certain

An expert from Tel Aviv University in Genetics

APOE epsilon 4 is a major risk factor and several smaller associations have been found since.

 

Is alzheimers genetic?

Håkan Thonberg has answered Near Certain

An expert from Karolinska Institutet in Genetics

It is certain that some forms of Alzheimer disease (AD) are genetic in the sense that they are caused by variations in the genome, so called mutations. Usually such forms of AD, have an onset Before the age of 65. Also, these forms of AD aggregates in families with a pattern that suggests it to be inherited in a dominant autosomal way. Other forms of AD may occur later in life and appear more sporadic among individuals in a family, or in single individuals. Such forms are less genetic, and the influence of inheritance are regarded to cause elevated risk for the disease, as opposite to be causative. So, the answer is yes, but the degree of genetic influence varies from being very small, or even absent, to being 100%.

 

Is alzheimers genetic?

Rebecca Sims has answered Near Certain

An expert from Cardiff University in Genetics

The answer to this question depends on the form of Alzheimer’s disease. There are forms that segregate in families that are caused by genetic mutations in the APP, PSEN1 or PSEN2 genes. However, these forms are very rare. For the common (~99% of cases), late onset form of Alzheimer’s I completely agree with Ali Torkamani, genetics contributes between a 56% and 79% susceptibility to disease development. A number of other factors, including age, affect an individuals risk of disease onset.  

 

Is alzheimers genetic?

Jolanta Dorszewska has answered Likely

An expert from Poznan University of Medical Sciences  in Neuroscience, Neurobiology, Genetics

Alzheimer’s disease is multifactorial genetic and environmental

 

Is alzheimers genetic?

Silva Hecimovic has answered Near Certain

An expert from Ruder Boskovic Institute in Neurobiology, Alzheimer’s Disease, Neurodegenerative Disease

The genetics that we inherit determines how we respond to different stimuli. This interrelationship makes Alzheimer’s disease (AD) a complex disorder, since stimuli are needed to enable genetically-based expression of AD. In constrast to the most common form of AD, in a rare familial form, AD is expressed purely by a genetic component and the inherited mutation, no stimuli are needed.

 

Is alzheimers genetic?

Cynthia Picard has answered Near Certain

An expert from Douglas Mental Health University Institute in Alzheimer’s Disease, Genetics, Biochemistry

Genetic variants in the genes APP, PSEN1 and PSEN2 are known to cause familal Alzheimer’s disease. For the sporadic form, the strongest genetic risk factor is the E4 allele of the Apolipoprotein E gene. Other factors such as age, gender and cholesterol-related medical conditions also influence the risk.

 

Is alzheimers genetic?

Arthur W Toga has answered Likely

An expert from University of Southern California in Neuroimaging

Yes partly. certain mutations can (with varying degrees) increase the likelihood of developing AD. A number of these have been identified. there is also a familial form of dementia caused by rare, inherited gene mutations that result in AD often before the age of 60.

 

Is alzheimers genetic?

Tengfei Wang has answered Likely

An expert from University of Tennessee Health Science Center in Neurodegenerative Disease, Neuroscience, Pharmacology, Genetics, Medicine

Unfortunately, the cause of Alzheimer’s disease is still largely unknown right now.

Alzheimer’s disease(AD) has two types, the so termed early onset familial AD(<60 years of age) and sporadic AD(>65 years of age).

The early onset familial AD is in autosomal dominant inheritance and can be attributed to the genetic mutations of amyloid precursor protein (APP) and presenilins 1 and 2[PMID: 18332245].

Sporadic AD is considered as a multifactorial disease. The risk factors include environmental and genetic differences. The best known genetic risk factor is APOEε4 allele [PMID: 16876668]. More AD related polymorphisms of genes were discovered by genome-wide association (GWAS) studies.