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Harvard Health Blog
A clue to a cure for Alzheimer’s disease
- By Andrew E. Budson, MD, Contributor; Editorial Advisory Board Member, Harvard Health Publishing
Are you worried about Alzheimer’s disease? Does one of your parents or siblings have the disease? If so, your risks are between two and four times that of the general public. What about people without a family history of the disease? Unfortunately, everyone is at risk for it. By age 85, half of you reading this article today will have developed Alzheimer’s disease, with or without a family history.
Sounds pretty scary, doesn’t it?
I’m writing today to give you some good news. A new study from the lab of Harvard researcher Yakeel Quiroz, PhD, has suggested a new target for drugs that might have the potential to slow down or even stop Alzheimer’s disease in its tracks.
A family with early-onset disease — and one exception
Dr. Quiroz, her longtime colleague Dr. Francisco Lopera, and first author Dr. Joseph Arboleda-Velasquez have been studying a large family in Colombia, South America, some of whom have a mutation in the presenilin 1 gene that causes early-onset Alzheimer’s disease. Over 1,000 people in this family are affected by the mutation. Among these family members, early symptoms of Alzheimer’s, such as memory loss and word-finding difficulties, almost always develop around age 44, and dementia follows at around age 49. Sometimes individuals may develop these symptoms or dementia one, two, or even three years later. But not 10 or 20 years later — and certainly not 30 years later. Yet one individual — a woman in her 70s with this genetic mutation — is only now starting to show symptoms.
The study, reported in the November 2019 issue of Nature Medicine, is a case report and extensive analysis of this one woman.
The APOE gene can modify your risk of Alzheimer’s
Many people have read or heard about variations in the APOE gene as a risk factor for Alzheimer’s. Interestingly, in their inquiry into why this woman with a mutation for early-onset Alzheimer’s had not yet developed dementia, the researchers found that she had an additional mutation in her APOE gene.
APOE has been linked to ordinary, late-onset Alzheimer’s disease and comes in three common forms. Most people, about 70% to 75%, have APOE3. About 15% to 20% of people have an APOE4 gene, and about 5% to 10% of people have an APOE2 gene.
- If you have one APOE4 gene, your risk of developing Alzheimer’s disease is three to four times more likely than if you only have APOE3 genes.
- If you have one APOE2 gene, your risk of developing Alzheimer’s disease is somewhat less than if you only have APOE3 genes.
This woman’s mutation of her APOE gene is an unusual variant called APOE3Christchurch (APOE3ch), named after the New Zealand city where it was first discovered. Even more unusual is the fact that she had two versions of this mutation, meaning that both her father and her mother gave it to her. The researchers wondered if this APOE3ch mutation could be the cause of her resistance to Alzheimer’s disease.
Resistance to tau
Another piece of the puzzle relates to an abnormal protein called tau. Tau is associated with the destruction of brain cells in Alzheimer’s disease. Tau is thought to accumulate in the brain after amyloid protein — the pathologic hallmark of Alzheimer’s disease — forms plaques. Although her brain was full of abnormal amyloid plaques — even more so than most people with full-blown Alzheimer’s dementia — she had relatively little tau.
Now the question was, could the APOE3ch mutation be related to the small amounts of tau protein? Although the answer is far from settled, the researchers did uncover some clues through laboratory experiments. Their findings suggest that the APOE3ch mutation may reduce the uptake of tau in brain cells. In addition, they were able to produce similar beneficial results using a special protein they created in the laboratory to try to mimic the effects of the APOE3ch mutation.
Where we are now
In brief, these Harvard researchers have a viable hypothesis to explain why this woman has been highly resistant to developing Alzheimer’s disease dementia. Moreover, their work suggests a possible path to a treatment that could be beneficial for all forms of Alzheimer’s disease.
We are still years away from a human treatment. The next step will be to try to treat laboratory models of Alzheimer’s disease in rodents, and then clinical trials in people with the disease after that. But in my view, this paper has provided the scientific community with a clue that may lead us to an eventual cure for Alzheimer’s disease.
About the Author
Andrew E. Budson, MD, Contributor; Editorial Advisory Board Member, Harvard Health Publishing
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No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician.
You might also be interested in…
Alzheimer's Disease: A guide to diagnosis, treatment, and caregiving
Have you noticed memory problems piling up in ways that affect daily life in yourself or someone you love? Do you find yourself struggling to follow a conversation or find the right word, becoming confused in new places, or botching tasks that once came easily? More than 5 million Americans have Alzheimer’s disease, and estimates suggest it will affect 13.8 million by 2050. Already, it is the sixth leading cause of death in the United States. This Special Health Report, Alzheimer's Disease: A guide to coping, treatment, and caregiving, includes in-depth information on diagnosing Alzheimer’s and treating its symptoms.
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