Alzheimer disease

Symptoms

What are the main symptoms of Alzheimer Disease?

Alzheimer Disease (AD) is a common cause of dementia. It begins with general forgetfulness, but this can lead to memory loss and impaired judgment. People with more advanced symptoms can feel lost or confused by regularly visited places and common activities. People with AD may lose the ability to live independently. Changes to behavior are reported as well, and people may react inappropriately in social situations. Impatience, agitation, and withdrawal are described as symptoms. Symptoms of Alzheimer Disease can start as mild but typically progress over time.

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Are there early onset or late onsets of Alzheimer Disease?

Is there variable expression or incomplete penetrance in familial Alzheimer Disease?

Is familial Alzheimer Disease always early onset?

Are there early onset or late onsets of Alzheimer Disease?

There is a range in when symptoms of Alzheimer Disease present. Most often people are older than 65 years old when they begin noticing symptoms of Alzheimer Disease, but in some cases, the symptoms appear earlier. Typically, it is described as “early onset” if the diagnosis is before age 65. Less than 5% of cases are thought to be early onset. The other 95% is late onset. Any diagnosis after age 65 is considered late onset. Sometimes it is difficult to figure out exactly when symptoms started.

Is there variable expression or incomplete penetrance in familial Alzheimer Disease?

The question of whether or not there is variable expression or incomplete penetrance in familial Alzheimer Disease is dependent on which gene has a change (mutation) that causes it. There are three genes that cause early onset Alzheimer Disease: PSEN1, PSEN2, and APP. There is another gene, APOE, that is associated with an increased risk for late onset Alzheimer Disease.

PSEN1 gene: Familial AD caused by mutations to the PSEN1 gene has nearly complete penetrance. This means that nearly all people with a disease-causing change in this gene will develop AD.

PSEN2 gene: Familial AD caused by mutations in the PSEN2 gene has around 95% penetrance. This means that 95% of people with a disease-causing change in this gene will develop AD. This means 5% of people who have a change in this gene will not develop symptoms of Alzheimer Disease.

APP gene: Familial AD caused by mutations in the APP gene does not have complete penetrance although the exact numbers are not known at this time. This means not everyone will an APP disease causing change will develop Alzheimer's disease although the chances are very high.

APOE gene: Having a change to APOE does not confirm or rule out that a person will have Alzheimer Disease. Certain changes to APOE (mainly APOe4 allele) can raise the risk to develop Alzheimer Disease. There is no way to accurately predict whether someone with an APOe4 allele will develop Alzheimer disease or not. This is why genetic testing of the APOE gene is not recommended at this time.

All of the genes can show variable expression. This means that different people with the same genetic change will show different symptoms at different ages. Even within the same family people can develop Alzheimer Disease at different ages. In some people the disease progresses quickly and in others it progresses more slowly. Some people present with different symptoms than other family members.

Is familial Alzheimer Disease always early onset?

Twenty-five percent of all Alzheimer Disease is thought to be Familial. Familial means more than 2 closely related family members are affected with Alzheimer Disease. Familial Alzheimer Disease is not always have symptoms that start at an early age. Familial Alzheimer Disease caused by genetic changes to the APOE gene causes symptoms at a later age. This means that generally the onset of symptoms is after 65 years old. Up to 98% of people with Familial Alzheimer Disease have later onset of symptoms. Less than 2% of people with familial Alzheimer syndrome have early onset of symptoms. Most cases of Familial Late Onset Alzheimer Disease cannot be explained by a single gene.

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