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Is There A Genetic Link To Alzheimer’s

Low Testosterone Linked To Dementia And Alzheimers Risk In Large Study

Alzheimers & Genetics (Is There a LINK?)

A large study involving almost 160,000 people has suggested that low testosterone in older men has a link to dementia and Alzheimer’s disease. The researchers did not find a causal link, so the nature of this relationship is not known, but the paper is one of the sturdiest pieces of evidence that has highlighted this connection yet.

The research was recently published in the journal Alzheimers and Dementia. Scientists led by the University of Western Australia in Perth sifted through data from the UK Biobank, an open-access biomedical database containing in-depth genetic and health information from half a million people in the UK. From this repository of data, they looked at 159,411 men aged between 50 and 73, up to 826 of whom had developed dementia, including 288 with Alzheimers disease.

After adjusting for other variables, they found that the older men with lower testosterone were significantly more likely to have dementia and Alzheimers disease.

Testosterone is the male sex hormone associated with sex drive, muscles, aggression, and sperm production. Women also produce testosterone, but at significantly lower levels than men.

Cause #: Past Head Trauma

The Alzheimers Association states that scientists have found a link between traumatic brain injury and a greater risk of dementia. After a traumatic injury, your brain creates large amounts of beta amyloid. This is the same protein that develops into the damaging plaques that are a hallmark of Alzheimers.

Theres one difference: After a traumatic brain injury, beta amyloid, although present, doesnt clump into plaques. However, the damage may increase the risk of them doing so later in life.

Alzheimers Disease And Inflammation

While Alzheimers is primarily characterized by a harmful buildup of amyloid protein and tangles in the brain, there is also extensive inflammation in the brain that highlights the importance of the immune system in Alzheimers, explains Dr. Dervis Salih.

Dr. Salih is a senior research associate in neurodegenerative disease at University College London .

In previous work by UCL, genetic studies revealed that different genes can alter the risk of developing Alzheimers disease. These risk genes change how microglia, or immune cells of the brain, respond to amyloid protein and tangles.

Scientists have focused on a subpopulation of microglia cells known as , which increase with age and in response to amyloid proteins.

IRM cells respond to interferon proteins that the body releases to fight viral infections, such as SARS-CoV-2.

According to Dr. Rosa Sancho, head of research at Alzheimers Research UK, Fairy early in the pandemic, people with dementia emerged as a group at particular risk of severe COVID-19.

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Who Can Take A Diagnostic Genetic Test

To see whether genetic testing might be useful, the doctor will collect information on the persons medical history and that of their close family. If possible, the doctor will collect information on at least three generations of the family. The medical history will include details of:

  • any family members diagnosed with dementia
  • any family history of mental illness
  • any family history of strokes or neurological conditions .

Diagnostic testing for familial dementia is only normally recommended if the person has developed symptoms very early on or if there is a particular familial pattern.

If the doctor does not find a strong family history of dementia, they will not recommend that the person take a diagnostic genetic test.

Predictive testing for dementia

Genes And Vascular Dementia

Punnett

Vascular dementia is caused when blood flow to the brain is reduced, damaging nerve cells. This can happen as a result of a stroke or damage to blood vessels deep in the brain. The majority of cases of vascular dementia are not caused by faulty genes.

We may carry genes that affect our risk of stroke, heart disease or other diseases that may contribute to vascular dementia. However, lifestyle factors such as smoking, lack of exercise, obesity, drinking alcohol over the recommended limits, and an unbalanced diet can also affect our risk.

There are rare genetic disorders that can cause vascular dementia by damaging blood vessels in the brain. One is called CADASIL and can be passed down through families. CADASIL only affects around 1,000 people in the UK.

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Snps Associated With Oas1 Are Linked To Risk For Alzheimers Disease And Critical Illness With Covid

Our recent work overlapping the mouse amyloid-associated transcriptome network with human gene-level-aggregated Alzheimers disease risk variants, identified a microglial co-expression network, whose eigengene strongly correlated with the level of amyloid- pathology and contained the mouse orthologues of many known human GWAS loci . This work also predicted the importance of several previously unidentified risk genes, including OAS1, and demonstrated a co-localization between Alzheimers disease risk loci and expression quantitative trait loci regulating OAS1 expression in: human iPSC-derived macrophages stimulated with a combination of IFN- and salmonella and human monocytes stimulated with lipopolysaccharide or 5-triphosphate dsRNA.,, To evaluate Alzheimers disease-associated genetic variation in OAS1, we genotyped the top SNP, rs1131454, identified by our gene-level analysis of the Lambert et al. GWAS. SNP rs1131454 was genotyped in 1313 individuals with sporadic Alzheimers disease and 1234 control individuals that were not included in the original cohort from Lambert et al. We found a significant association of rs1131454 with Alzheimers disease in this independent cohort of Alzheimers disease and control individuals .

When Is Genetic Testing For Dementia Appropriate

In some cases, it may seem likely that a persons dementia is caused by a single-gene change for example, if the person has a very strong family history of dementia. In these cases, it may be appropriate to offer genetic testing to the person and to their family.

However in most families dementia will not be caused by a single-gene change. In these cases, genetic testing will not be appropriate. This is because testing for risk variants does not provide any certainty about the persons chances of developing dementia.

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Genetic And Lifestyle Risk Factors

The short answer is that the risk of developing dementia is related to a combination of genetics and lifestyle, with age being the biggest risk factor.

In most cases, genetic risk factors come from small influences of many genes, rather than one mutation being responsible for the entire genetic effect. Therefore, it is unlikely that a child will inherit every dementia-related mutation that a parent has.

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AD2: APOE

Inheritance and clinical features

The APOE gene has been associated with both familial late-onset and sporadic late-onset AD in numerous studies of multiple ethnic groups. The APOE4 genotype is associated with higher risk of AD, earlier age of onset of both AD and Down syndrome , and a worse outcome after head trauma and stroke, both in humans and in transgenic mice expressing human APOE4. The frequency of the APOE4 allele varies between ethnic groups, but regardless of ethnic group, APOE4 carriers are more frequently found in controls and APOE4+ carriers are more frequently found in patients with AD.,

Gene location and structure

Apolipoprotein E structure and single nucleotide polymorphisms . The general protein structure of APOE is shown. The 2 SNPs in exon 4 and corresponding protein locations are shown . The 3 APOE 4 alleles are defined by 2 SNPs, rs429358 and rs7412, with 2 defined by nucleotides T-T 3 defined by T-C, and 4 defined by C-C, respectively.

Gene function and expression

The mechanisms that govern apoE toxicity in brain tissue are not fully understood. Some proposed mechanisms include isoform-specific toxicity, APOE4-mediated amyloid aggregation, and APOE4-mediated tau hyperphosphorylation.

In addition, individuals carrying APOE4 have higher amyloid and tangle pathology and an increase in mitochondrial damage compared to those carrying other APOE polymorphisms.

Genetic variation

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Genes And Dementia With Lewy Bodies

Dementia with Lewy bodies is caused by a build-up of abnormal proteins in the brain and may have symptoms similar to those seen in Parkinsons disease. Age is currently the biggest known risk factor for dementia with Lewy bodies, although research is underway to find out whether genes may also play a role.

Do Genes Cause Diseases

Genetic mutations can cause diseases. If a person inherits a genetic mutation that causes a certain disease, then he or she will usually get the disease. Sickle cell anemia, cystic fibrosis, and some cases of early-onset Alzheimer’s disease are examples of inherited genetic disorders.

Other changes or differences in genes, called genetic variants, may increase or decrease a person’s risk of developing a particular disease. When a genetic variant increases disease risk but does not directly cause a disease, it is called a genetic risk factor.

Identifying genetic variants may help researchers find the most effective ways to treat or prevent diseases such as Alzheimer’s in an individual. This approach, called precision medicine, takes into account individual variability in genes, environment, and lifestyle for each person.

The expression of geneswhen they are switched on or offcan be affected, positively and negatively, by environmental and lifestyle factors, such as exercise, diet, chemicals, or smoking. The field of epigenetics is studying how such factors can alter a cell’s DNA in ways that affect gene activity.

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Genetic Testing And Counseling

In contrast, EOFAD, with an age at onset before 60 to 65 years old, has an autosomal dominant mode of inheritance in which 20% to 70% of cases are estimated to have a PSEN1 mutation, 10% to 15% of cases are estimated to have an APP mutation, and PSEN2 mutations are rare., Indeed, approximately 60% of patients with EOAD have another known affected family member. The remaining 40% of patients with EOAD may lack a family history because of an early death of a parent, failure to recognize the disorder in family members, or, very rarely, a de novo mutation. If the parent of a patient with EOAD has a mutant allele, then the risk to the patients sibling of inheriting the mutant allele is 50%. The child of a patient with EOAD who carries a mutation has a 50% chance of transmitting the mutant allele to each of their children.

In this article, we have reviewed the genetics of AD. Further molecular genetic investigations should clarify the roles of additional known genes in the pathogenesis of both common sporadic as well as rare familial forms of AD. Already, investigations of the normal and aberrant functions of A protein and ApoE has provided insight into the underlying mechanisms for AD. Such research will continue to provide new strategies for therapeutic interventions.

Other Types Of Dementia

The APOE Genetics of Alzheimers Disease  Alzheimer

Different types of dementia are affected by genetics to varying extents. For example, young onset dementia is more likely to be hereditary the earlier a person develops dementia, the more likely it is due to a mutated gene.

Frontotemporal dementia is the second most common type of dementia that affects people under the age of 65. Around 40% of people with FTD have one or more close relative with a dementia of any type, not necessarily FTD. People with a family history of FTD may have genetic FTD, which is caused by a single genetic mutation.

Familial prion diseases are a group of very rare conditions inherited from dominant faulty genes. These diseases include Creutzfeldt-Jacob disease and cause dementia very rapidly.

People with Down syndrome are much more likely to develop dementia than the general population. This is because the APP gene is located on chromosome 21, which most people with Down syndrome have three copies of.

Huntingtons disease is an inherited condition that causes dementia. Unlike in FAD, the mutated gene here is not dominant, so people whose parents have Huntingtons disease only have a 50% chance of developing the disease themselves. It is almost unheard of to develop Huntingtons disease if neither of your parents have it.

Whatever genes you have, leading a healthy lifestyle can both reduce your chances of developing dementia and slow down the rate of progression if you do have dementia. Read more about keeping your brain healthy here.

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Dementia Caused By A Single

Of the four most common types of dementia, frontotemporal dementia is most likely to be caused by a single-gene change.

Is dementia different when it’s caused by a single-gene change?

Yes, it can be different in some ways.

  • It often develops earlier in life. For example, an affected person might get dementia in their 40s or 50s rather than in their 70s or above. This is known as young-onset dementia.
  • It tends to run strongly in families, with several close relatives who develop the same type of dementia. For example, a person with a single-gene dementia may have a grandparent, a parent and a brother who all had frontotemporal dementia . This is why dementia caused by a single-gene disease is sometimes known as familial dementia.

Can single-gene dementias be inherited directly?

Yes. If a single-gene dementia is present in a family, it is quite likely that a person from that family will develop dementia:

  • If one of the parents carries the changed gene, each child has a 1 in 2 chance of inheriting it.
  • If one of the children carries the changed gene, any brothers or sisters they have has a 1 in 2 chance of carrying it as well.

The Role Of Genetics In Advancing Precision Medicine For Alzheimers Diseasea Narrative Review

  • 1Litwin-Zucker Center for the study of Alzheimers Disease, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States
  • 2Division of Geriatric Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, United States
  • 3Robert S Boas Center for Genomics and Human Genetics, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, United States

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Adhd And Cognitive Decline

The study examined more than two million people born in Sweden between 1980 and 2001, of whom around 3.2% were diagnosed with ADHD. The researchers used national registries to link these individuals to more than five million biological relatives, including parents, grandparents, and uncles and aunts.

When they looked into whether these relatives developed dementia, they discovered that parents of individuals with ADHD had a 34% higher risk of dementia than parents of individuals without ADHD. The risk of Alzheimer’s disease, the most common type of dementia, was 55% higher in parents of individuals with ADHD.

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Experts welcome further research on the link between dementia and ADHD, but other areas of study are equally important. For instance, Dr. DeSilva believes the effect of trauma on the development of ADHD needs more attention. “Clearly, trauma affects brain developmenteven halting it in some areas of the brain,” she says. Because ADHD is a neurodevelopmental disorder, trauma may be a significant reason why some children develop ADHD, or do not “grow out of it.”

“Many symptoms of ADHD are the same as when a child is anxious or depressed ,” Dr. DeSilva adds. “Understanding this connection between brain development, mood, trauma, anxiety, and attention will help us develop treatments and preventive interventions to promote the health and wellbeing of our children.”

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What Are The Genetic Ties To Alzheimers Disease

Our genes carry the code that determines which of our parents traits we will inherit. Genes are found in each of the billions of cells that make up our bodies. We receive one gene copy from each parent. Those differences are what contribute to our uniqueness.

Lets say, for example, that your mother is very tall and your father has brown eyes. You could inherit the trait for her height, as well as the trait for his eye color. Your sibling might inherit the opposite combinationyour fathers height and your mothers eyes.

Our genetic code can also increase our individual risk for developing certain diseases and chronic health conditions. Sickle cell anemia, Huntingtons disease, and cystic fibrosis are all linked to an inherited single gene disorder.

Unfortunately, the genetic risks associated with Alzheimers arent as straightforward. Largely because so much of the science behind this disease continues to baffle researchers.

What we do know is that there are two types of Alzheimers disease, early-onset Alzheimers and late-onset Alzheimers. Early-onset, also known as familial Alzheimers disease , has a genetic link.

Information About Genetic Testing

Having a test to look for a faulty gene that causes dementia is only appropriate for a very small number of people. This is because inherited dementia is rare.

If you are worried that you have a strong history family of early-onset Alzheimers disease or frontotemporal dementia, you can speak to your doctor about this.

Not all gene mutations that cause dementia have been identified, meaning that some families may have many affected members, but no mutation can be found. Therefore, a negative test result cannot always rule out a genetic cause of a disease.

If a test is appropriate, your doctor should be able to refer you to a genetic counsellor or specialist. This could be a cognitive neurologist or memory clinic psychiatrist. They will discuss with you the pros and cons of taking a test and what will be involved. They will also tell you where the results will be kept, who they will be shared with, and what the next steps would be. For people found to have a genetic mutation that causes dementia, these discussions will also cover the options available if you are considering starting a family.

To find out more about genetic testing and what support is available you can visit www.raredementiasupport.org or call 020 3325 0828. Leave a message and you will be referred to the most appropriate team member.

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