Is Alzheimer's disease genetic?
-A middle school student from New Jersey April 21, 2011 Yes and no. Genes can play a large part in whether or not someone ends up with Alzheimer's disease. But they aren't the whole story. Other non-genetic factors can play a role too. In about 5% of cases, Alzheimer's is almost totally genetic. People inherit genes from their parents that cause them to end up with the disease at a very early age. This "early onset" Alzheimer's isn't the one most people think about, though. The other form, late onset Alzheimer's, is the more common type that kicks in later in life. It can happen in lots of different ways. Sometimes genes can play a big role and sometimes not. When genes aren't involved, other factors like exercise, blood pressure, doing puzzles and lots of things we don't know about yet contribute to our risk of getting Alzheimer's. Your risks depend on what genes you have and how you live your life. You can think of whether or not someone gets Alzheimer's disease like a set of scales. All of the different contributors to Alzheimer's--genes, exercise, and blood pressure are different sized weights that get put on one side of the scale or the other. One side of the scale tips you toward Alzheimer's disease, one side tips you away from it. People who have early onset Alzheimer's have heavy genetic weights that automatically tip the scales all the way to the Alzheimer's disease side. No amount of other protective genes or lifestyle changes will weigh enough to tip it back. Other genes are more like a medium or a light weight. Sometimes they can push you away from Alzheimer's and sometimes they can push you towards it. If you have lots of genes that would tend to push you toward Alzheimer's disease, then your scale will tip toward Alzheimer's disease. Lifestyle changes like lowering your blood pressure, doing puzzles, etc. can add weights to the other side of the scale. Your chances for Alzheimer's depend on how these factors all balance together. The same thing applies if you have a lot of genes that protect you from Alzheimer's disease. You'll tip away from Alzheimer's but having high blood pressure, not getting exercise, etc. could add weights to the Alzheimer's side. Again, your chances depend on how everything balances out. All of this is why Alzheimer's disease is what we call a complex disease. Its causes are, well, complex. Genetics certainly plays a role, but non-genetic factors weigh in too. And Alzheimer's isn't the only disease like this. It turns out that most common diseases like heart disease, diabetes, asthma, and many others are due to both genetic and non-genetic causes. The interesting thing about Alzheimer's disease is that sometimes it is caused by genetics alone. But most of the time we don't know whether genes, other causes, or both are to blame. Let's take a closer look at what Alzheimer's disease is and how genes are involved. A Common but Poorly Understood Brain Disease Alzheimer's disease is a condition that affects the brain. The symptom that most people probably think of is forgetfulness. But since Alzheimer's is degenerative, its symptoms get much worse over time. At first people with Alzheimer's disease have trouble remembering new things. Eventually though, they are unable to remember anything and they often can't speak, eat, or care for themselves. No one knows for sure what causes the symptoms of Alzheimer's disease. If you look at the brain of a person with Alzheimer's, you find clumps of protein inside and outside the brain cells. Scientists think that these clumps cause the brain cells to stop communicating with each other properly, but we don't know for sure. Eventually the brain cells shrink and die. Alzheimer's disease is very common. About 10% of all of us will develop it at some point. Early symptoms usually don't appear until your 70's or 80's, but sometimes it happens much earlier. Again, these early onset cases are where genetics plays the biggest role. Getting Alzheimer's Early Rarely, someone has "early-onset familial Alzheimer's disease." These are cases of Alzheimer's that run in families and happen much earlier than we would expect. Symptoms usually start when a patient is in his or her 40's or 50's. This kind of Alzheimer's disease is caused by genetics alone and is passed down through the family in a predictable pattern called autosomal dominant inheritance. In any one family, the disease is caused by changes in just a single gene. There is a fifty/fifty chance that someone with this type of Alzheimer's disease would pass on the changed copy to their children. On our scale these genes are the very heavy weights, since having mutations in just one of these genes means individuals will develop the disease. We currently know of three genes that can lead to early-onset familial Alzheimer's disease: APP, PSEN1, and PSEN2. Individuals with a change in one of these genes will definitely get Alzheimer's disease if they live into their 40's and 50's. It turns out that all three of these genes are important in the formation of the protein clumps that are found in the brains of those with the disease. One of them (APP) even has the instructions for one of the proteins that clumps! There are also families that follow the early-onset familial pattern of Alzheimer's disease but don't have changes in APP, PSEN1, or PSEN2. This means there are probably other early-onset heavyweight genes that we just haven't identified yet. As I said before, these early-onset cases are rare. Having mutations in one of these early-onset genes tips the scale strongly towards Alzheimer's disease, but they account for less than 2% of the cases. So, what about the other 98% of the cases? Most Cases of Late Alzheimer's are Complicated

About 10% of us will
develop Alzheimer's.
Around 15-25% of Alzheimer's cases can be called "late-onset familial." The symptoms in these cases occur at the same age as other cases of Alzheimer's disease. But unlike most other cases, the disease tends to cluster in the family. One gene that we know can be involved in late-onset familial cases is APOE. Specific changes in the APOE gene are known to greatly increase the chances that someone will develop Alzheimer's disease. But, unlike the early-onset genes, you can't predict who will develop the disease just based on what their APOE gene looks like. This is probably because changes in other genes help determine whether someone will get Alzheimer's disease or not by tipping the scale in either direction. There are at least a dozen other genes under investigation that might be linked to Alzheimer's disease. With that many genes weighing in it is clear why we call Alzheimer's disease a complex disease! But that still leaves 73-83% of cases unexplained. These are the cases of Alzheimer's disease that don't cluster in families, or what we call the sporadic cases. This is where non-genetic causes probably play the biggest role, and genetic causes only tip the scale slightly or not at all. We know that things like diet and exercise are important non-genetic factors in other complex diseases like heart disease and diabetes. Much less is known about the non-genetic factors in Alzheimer's disease. It looks like keeping your blood pressure down, eating healthy, doing physical exercise, and keeping your mind busy may all help to decrease your chances of getting Alzheimer’s disease. So where does that leave us? Remember the scales. All of the different contributors to Alzheimer's disease--genes, exercise, and blood pressure--are different sized weights that tip you toward or away from Alzheimer's disease. APP, PSEN1 and PSEN2 are the heaviest weights. If they get put on your scale then it tips all the way to the Alzheimer's disease side. No amount of other protective genes or lifestyle changes will weigh enough to tip it back. APOE is a medium weight. If you have some other medium or light weight genes that would tend to push you toward Alzheimer's disease, then you'll tip further toward Alzheimer's disease. If you have a lot of genes that protect you from Alzheimer's disease, then you'll tip in the other direction. Other factors like having a healthy lifestyle and doing puzzles may also add weights away from the Alzheimer's disease side. How big of a role genetics plays in any one case of Alzheimer's disease depends on how many weights you have and how heavy they are. Video about how Alzheimer's disease progresses. Sarah Garcia

Different genes and
environmental factors
can tip you towards
or away from Alzheimer's.

For most cases, the causes of
Alzheimer's are not
yet well understood.