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What Gene Causes Early Onset Alzheimer’s

Genes And Dementia With Lewy Bodies

Living with early onset Alzheimer’s disease

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.

The Mutation Spectrum Of Psen1

Patients with PSEN1 mutations typically have an earlier age of onset, with symptoms starting an average of 8.4 years earlier than in APP mutation carriers and 14.2 years earlier than in PSEN2 mutation carriers . Other studies have shown that very early-onset AD , which starts before the age of 35 years, is almost entirely caused by PSEN1 mutations . Like APP, mutations in the promoter region of PSEN1 also were found to be associated with increased risks of EOAD, perhaps due to an alteration of PSEN1 gene expression with a subsequent influence on A load . Seizures and myoclonus is common feature of autosomal dominant EOAD, which was associated with PSEN1 mutation .

What Is Early Onset Familial Alzheimer Disease

Definition: What Is eFAD?

Early onset familial Alzheimer disease is hereditary and marked by Alzheimer disease symptoms that appear at an unusually early age. Symptoms can start in a person’s thirties, forties, and fifties . Generally, if you are diagnosed with eFAD, then one of your parents will also have had it if he or she lived long enough, and your siblings and your children may have a 50-50 chance of having inherited it. Very rarely, eFAD can make a first-time appearance in a family through a new genetic mutation.

Genetics researchers studied eFAD families to discover the three known genes that cause familial AD: amyloid precursor protein , presenilin-1 , and presenilin-2 . Of these, PS1 mutations account for most eFAD, while APP and PS2 are more rare. Having a pathogenic mutation in one of these three genes virtually guarantees that one will develop early onset Alzheimer disease. Tests can determine which gene is at fauly . There are also cases of eFAD that cannot be linked to one of these three genes. There may be additional genes waiting to be discovered, if only researchers could connect with more eFAD families.

Prognosis: Is eFAD Different from LOAD?

How Common Is Early Onset Familial Alzheimer Disease?

For practical and research purposes, doctors and scientists need defined populations for study and the numbers change based on the definitions. The definition would seem to rest on two criteria:

Early onset sporadic Late-onset sporadic

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Risk To Family Members Nonfamilial Alzheimer Disease

Genetic counseling for people with late-onset nonfamilial AD and their family members must be empiric and relatively nonspecific. First-degree relatives of a person with nonfamilial AD have a cumulative lifetime risk of developing AD of approximately 15%-39%, which is typically reported as a 20%-25% risk . This risk is approximately two to three times that of the .

Disagreement exists as to whether the age of onset of AD in a person with nonfamilial AD changes the risk to first-degree relatives. found that the risk to relatives of a with nonfamilial AD decreases with increasing age of onset of the proband.

Health Environmental And Lifestyle Factors That May Contribute To Alzheimer’s Disease


Research suggests that a host of factors beyond genetics may play a role in the development and course of Alzheimer’s disease. There is a great deal of interest, for example, in the relationship between cognitive decline and vascular conditions such as heart disease, stroke, and high blood pressure, as well as metabolic conditions such as diabetes and obesity. Ongoing research will help us understand whether and how reducing risk factors for these conditions may also reduce the risk of Alzheimer’s.

A nutritious diet, physical activity, social engagement, sleep, and mentally stimulating pursuits have all been associated with helping people stay healthy as they age. These factors might also help reduce the risk of cognitive decline and Alzheimer’s disease. Clinical trials are testing some of these possibilities.

Early-life factors may also play a role. For example, studies have linked higher levels of education with a decreased risk of dementia. There are also differences in dementia risk among racial groups and sexesall of which are being studied to better understand the causes of Alzheimers disease and to develop effective treatments and preventions for all people.

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Stopping Alzheimers Before It Starts

Study authors admit there is still no clear treatment for Alzheimers disease, the leading cause of dementia. Despite that, the team says their findings give Alzheimers researchers new insight into what initially triggers the disease.

The most exciting aspect of our study is that we have now honed in on a novel pathway that to date has not been explored in great detail. Additionally, our data suggest that modifying white blood cell function may be therapeutically relevant for progressive neurodegenerative conditions, study first author Dr. Conor Delaney explains.

It is absolutely critical that we focus our research endeavors on identifying the underlying cause of neurodegenerative conditions. Studies like these will pave the way for better clinical management of our patients and hopefully new medicines to treat the condition, concludes Colin Doherty, Professor of Epilepsy at Trinity.

Symptoms Of Early Onset Alzheimers Disease

Most people experience momentary memory lapses. Misplacing keys, blanking on someones name, or forgetting a reason for wandering into a room are a few examples. These arent definitive markers of early onset Alzheimers, but you may want to watch out for these signs and symptoms if you have a genetic risk.

The symptoms of early onset Alzheimers are the same as other forms of Alzheimers. Signs and symptoms to watch out for include:

  • difficulty following a recipe
  • frequently misplacing things without being able to retrace steps to find it
  • inability to balance a checking account
  • getting lost en route to a familiar place
  • losing track of the day, date, time, or year
  • mood and personality changes
  • trouble with depth perception or sudden vision problems
  • withdrawing from work and other social situations

If youre younger than 65 and experience these kinds of changes, talk with your doctor.

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Bgrowth Hormone Response To Growth Hormone

Results of several studies addressing this point show varied results: superimposable responses of GH to GHRH than responses of GH to GHRH in controls a blunted GH to GHRH response in AD patients higher GH concentrations in the morning and a greater increase of GH to GHRH in AD patients than in controls . More recent studies demonstrate the reduced release of GH to GHRH in AD patients . In general, investigations of GH-releasing stimulation tests, especially of GHRH in AD, are equivocal and, in some cases, contradictory. Factors that may contribute to the inconsistent findings include the variability of GHRH stimulated among control groups, the age and sex of patients, the lack of uniformity in test procedures, and the variability and the lack of reproducibility of the GHRH test either in controls or in AD patients .

Table II. Different Patterns of Response of GH to Its Stimuli in Alzheimer’s Disease Patients

1. Higher GH concentrations in the morning
2. Superimposable GH response to GHRH than GH response to GHRH in controls
3. Blunted GH response to GHRH in Alzheimer’s disease patients
4. Higher increase of GH after GHRH in Alzheimer’s disease patients
5. Blunted GH response to clonidine in Alzheimer’s disease patients, with higher levels of aggression

Leon E. Rosenberg, Diane Drobnis Rosenberg, in, 2012

Genetic Testing For Alzheimers Disease

Early Onset Alzheimer’s Disease: What Families and Patients Need to Know | UCLAMDChat

A blood test can tell which APOE gene you have, but the results canât predict whether youâll get Alzheimerâs. Doctors use these tests mostly for research purposes. The test can tell them who has certain risk factors so they can watch for brain changes in case the disease develops.

Doctors donât typically recommend genetic testing for late-onset Alzheimerâs because the results can be confusing and cause emotional distress. If youâre showing symptoms or have a family history, your doctor may recommend testing to help diagnose early-onset Alzheimerâs. Doctors can usually diagnose Alzheimerâs without a genetic test.

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Genes And Vascular Dementia

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.

Can Alzheimers Disease Be Inherited

In the vast majority of cases , Alzheimers disease is not inherited.

The most important risk factor for Alzheimer’s disease is age. Because Alzheimer’s disease is so common in people in their late 70s and 80s, having a parent or grandparent with Alzheimer’s disease at this age does not change your risk compared to the rest of the population.

However, if somebody has developed Alzheimers disease at an earlier age there is a greater chance that it may be a type of Alzheimers disease that can be passed on.

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Causes Of Early Onset Alzheimers

Most young people diagnosed with early onset Alzheimers disease have the condition for no known reason. But some people who experience early onset Alzheimers disease have the condition due to genetic causes. Researchers have been able to identify the genes that determine or increase your risk for developing Alzheimers.

The Genetic Architecture Of Eoad



The gene and protein structure of APP

The gene encoding APP is located on chromosome 21q21.3. It is a highly conserved gene containing 18 exons and spanning 290 kilobases . APP protein is a ubiquitously expressed single-pass type I transmembrane protein, with a large extra-membranous N-terminal region, a single transmembrane domain and a small cytoplasmic C-terminal tail . APP proteins range from 365 to 770 amino acids due to different splicing isoforms .

Alternative splicing of transcripts from the single APP gene results in several isoforms of the gene product. APP695, APP751 or APP770 are the most common APP isoforms . APP695 is preferentially expressed in the central nervous system. APP751 and APP770 expressed both in the peripheral and central nervous systems. The ratios of APP770 mRNA and APP770-plus-APP751 mRNAs were increased significantly in AD brain . Both APP751 and APP770 contain the Kunitz protease inhibitor domain, and APP770 also contains an OX-2 domain . APP695 on the other hand, lacks both of these domains. The up-regulation of the KPI-containing APP isoforms has been reported in the brains of AD patients and could be associated with the diseases progression . Except for the protease-inhibitor role of the KPI domain, no other definite functional differences have been found in the different APP isoforms . Other isoforms are referred to as leukocyte-derived APP . L-APP mRNA is either seldom or never expressed in the central nervous system tissues .

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Can Frontotemporal Dementia Be Inherited

Sometimes, yes. FTD is relatively rare compared with Alzheimers disease or vascular dementia, but it can be passed on directly from parent to child. A diagnosis of FTD can therefore cause a great deal of worry to someone who has children or grandchildren.

Most FTD is not directly inherited, but about 40 per cent of people who develop the condition will have at least one close relative diagnosed with some kind of dementia. This can include FTD, Alzheimers disease or amyotrophic lateral sclerosis . In general, the greater the number of relatives who have had dementia particularly FTD or ALS the greater the chances of developing familial FTD.

Of the different types of FTD, the behavioural form is the one that is inherited most often. The type of FTD which starts as primary progressive aphasia is only rarely inherited.

There are lots of different genes causing familial FTD, each with its own pattern of inheritance. If you are concerned about either passing on an FTD gene or inheriting the disease from your parents, you can ask your GP to refer you to a genetic testing service in your area. These people are specially trained to guide you through the process of finding out whether you have a gene that causes FTD. You can also get in touch with a specialist support group at Rare Dementia Support, who can provide information and advice about how to cope with having a heritable form of FTD in your family.

Key Points About Early

  • Alzheimer disease commonly affects older people, but early-onset Alzheimer disease can affect people in their 30s or 40s.

  • It affects memory, thinking, and behavior.

  • Although there is no known cure, early diagnosis and treatment can lead to better quality of life.

  • Stay healthy with a good diet and regular exercise.

  • Avoid alcohol and other substances that may affect memory, thinking, and behavior.

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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.

What Test Will Your Doctor Do To Diagnose Alzheimers

What is early onset Alzheimer’s disease?

No single test can confirm early onset Alzheimers. Consult an experienced physician if you have a family history of early onset Alzheimers.

Theyll take a complete medical history, conduct a detailed medical and neurological exam, and review your symptoms. Some symptoms may also seem like:

  • anxiety
  • alcohol use
  • medication side effects

The diagnostic process may also include magnetic resonance imaging or computed tomography scans of the brain. There may also be blood tests to rule out other disorders.

Your doctor will be able to determine if you have early onset Alzheimers after theyve ruled out other conditions.

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What Are The Symptoms Of Early

For most people with early-onset Alzheimer disease, the symptoms closely mirror those of other forms of Alzheimer disease.

Early symptoms:

  • Withdrawal from work and social situations

  • Changes in mood and personality

Later symptoms:

  • Severe mood swings and behavior changes

  • Deepening confusion about time, place, and life events

  • Suspicions about friends, family, or caregivers

  • Trouble speaking, swallowing, or walking

  • Severe memory loss

The Combined Effect Of Multiple Genes

Why is the inheritance of late-onset Alzheimers so much less frequent than for early-onset? In part, the answer is that there is no single gene mutation that consistently causes late-onset Alzheimers in the autosomal dominant pattern characteristic of early-onset AD. Instead, the late-onset form seems to represent the combined effect of multiple genes, each of which increases the risk a little. The best known of these, the apolipoprotein E gene , provides information that the body needs to make a protein that plays a role in the transport of fats and cholesterol throughout the body. The Greek letter epsilon followed by a number is used to name the parts of ApoEs three versions: ApoE2, ApoE3, and ApoE4. One ApoE gene copy is inherited from each parent, so any combination of two gene copies can be present. The 4 type has been linked with an increased risk for early or late onset AD, and people who have inherited two copies are at even greater risk. It is estimated that people with the two copies of the 4 gene are at 12 to 15 times the risk for AD compared to noncarriers.4 But inheriting one or even two ApoE 4 genes does not guarantee that AD will develop, nor does the absence of any 4 genes assure that AD will not develop. In African Americans, the relationship of ApoE genotype to AD inheritance risk is weaker than in European Ancestry populations.

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What Are The Causes Of Young

The causes of young-onset dementia are similar to the diseases that usually cause dementia in older people. However, some causes, such as frontotemporal dementia , are more common in younger people. Dementia in younger people often has different symptoms, even when its caused by the same diseases as in older people.There is more information about some common causes of dementia, and how they can affect younger people, below.

The Role Of Genetics: Will I Get Alzheimers Disease


Scientists are still trying to determine the underlying causes of Alzheimers disease. The hope is that one day we will be able to stop the disease from progressing or perhaps even prevent it altogether. To date, researchers have identified a few genes that play an important role in Alzheimers. Some of these genes are simply risk factors for Alzheimers disease. Other genes are hereditary and will cause Alzheimers disease to develop.

There are two types of Alzheimers disease: early-onset Alzheimers disease and late-onset Alzheimers disease. Early-onset Alzheimers disease is rare, occurring in people age 60 and younger. This represents less than 5% of all people with Alzheimers. One type of early-onset Alzheimers disease is known as autosomal dominant Alzheimers disease or early-onset familial Alzheimers disease . This is even more uncommon, affecting less than 1% of all people with Alzheimers. What makes this type of early-onset Alzheimers disease so unusual is that it is caused by a hereditary genetic mutation to one of three genes PSEN1, PSEN2, or APP.

A recent study examined data from 4 large, observational studies of adults ages 60 and older. The study reported the association between various APOE genotypes and the risk of developing mild cognitive impairment or dementia due to Alzheimers by age 85 as follows:

  • No family history of dementia
  • Being male

Factors that may increase a persons risk of developing Alzheimers include:

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