Dr. Patricia Yarberry Allen is a collaborative physician who writes a weekly “Medical Monday” column for Women’s Voices for Change.  (Search our archives for her posts, calling on the expertise of medical specialists, on topics ranging from angiography to vulvar melanoma.)

Today Dr. Allen calls on Dr. Richard S. Isaacson—Director of the Alzheimer’s Prevention Clinic, Memory Disorders Program at Weill Cornell Medical College/New York–Presbyterian Hospital—to give us an overview of what science knows so far about Alzheimer’s disease (AD) and why it strikes particular individuals.


adult helping senior in hospital

Why do some people develop Alzheimer’s disease? Some would say that that is the million-dollar question; others would call it the billion- or even trillion-dollar question. When it comes to AD, evidence shows that the disease may start in the brain more than 20 years before the first symptom of memory loss. 

Research and practicing clinicians realize, though, that not everybody will develop AD, but certain people are at higher risk than others. The No. 1 risk factor for AD is advancing age, and a variety of other factors like genetics, head trauma, and concomitant medical conditions (like diabetes) may also increase risk. 

Regarding genetics, some good news is that only 6 percent of AD cases are caused by the types of genes that can lead to early-onset AD (we will not get into technical detail here, but these genetic mutations include presenilin-1, presenilin-2, and amyloid precursor protein gene mutation). These genes may contribute to the development of AD in patients younger than age 60, although many younger-onset patients do not end up having these genes.

There is another set of genes associated with older-age onset of AD, or late-onset Alzheimer’s disease. The most well studied of these genes is called apolipoprotein epsilon-4  (commonly referred to as APOE4 [or APOε-4]). Briefly, we get one copy of the APOE gene from our mother and another copy from our father. There are three types of these genes, APOE2, APOE3, and APOE4. If a person has one or more of the APOE4s, the risk of developing AD will increase. However, genetic testing for APOE (or other genes for that matter) is not currently recommended. Knowing whether a person has one or more copies of APOE4 does not necessarily help a physician predict if or when a patient will develop AD. Conversely, having one or more copies of APOE2 confers a reduced risk of developing AD.  We still have a long way to go before using genetic testing to help with the pre-symptomatic diagnosis of AD. For these reasons, most doctors do not recommend genetic testing on family members of Alzheimer’s patients.

Regarding AD risk, a new study published in Nature this month offers what could be a groundbreaking step in the right direction.  This preliminary work may help to unlock some of the mysteries of why certain people develop AD, and others are more resistant to developing the disease, despite being at a variety of degrees of age-related or genetic risk.

In summary, the Nature study investigators examined the post-mortem brains of patients with dementia, and found that the brains of younger adults (20–35 years old) had low amounts of a protein that acts as a regulator for specific genes that promote brain aging and brain cell damage. This protein, called REST, was likely low during the younger years since there was not as much of a need for this protein at that young age. REST ‘works’ through protecting brain cells from normal aging processes (such as inflammation and oxidative stress).  As people aged, healthy older adults (73–106 years old) had a lot of this protein, and this suggests that since REST levels grew in those who ‘successfully’ aged without dementia, REST may be protective, related to brain (and body) longevity.

However, in patients with AD (as well as other cognitive impairments) this protein was not present in high amounts, suggesting that perhaps this protein was unable to protect the brain cells from damage, leading to cognitive decline. Unfortunately, there is not yet a way to measure REST levels in those people at risk for AD or those already diagnosed, but developing a marker (or even a substitute) could potentially lead to new avenues toward more reliable diagnosis, and more effective therapies, in the future.

Until we have more definitive results, people who are at risk for AD should speak to their treating physicians and discuss brain-healthy lifestyle options (including regular exercise, cognitive activities to keep the brain engaged, stress reduction, lifelong musical activities, and social engagement, as well as a comprehensive dietary and nutrition approach). In addition, medical problems related to increased AD risk (e.g., high blood pressure, diabetes) should be treated on an ongoing basis. There are a variety of other preventative strategies available, and several of these were covered in a January post.  We have made much progress in the fight against AD, and this new study is another step in the right direction.

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