A study published in Nature shows that a rare gene variant can protect against Alzheimer’s. By sequencing the genome of about 1,800 Iceland residents, scientists were able to show that a precursor protein responsible for the clumping accumulations of brain plaques known as beta amyloid may actually prevent the disease. This means if this variant could be duplicated through anti-amyloid drug therapy or other means it has the potential stave off Alzheimer’s.
Comparison of a healthy brain and one ravaged by Alzheimer's disease. Courtesy of National Institute on Aging (NIA)
Some scientists are hailing the study’s findings as a breakthrough. Given the potential significance, The Doctor’s Tablet editors asked Einstein’s aging and genetics researchers to assess the possible impact on future Alzheimer’s research and patient care.
Here is a sampling of opinion:
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Carrying genetic variants is not all about doom and gloom. They can also protect against disease.
There are 3 impressive features to this study. First, carrying a genetic variant in the amyloid precursor protein can reduce the production of smaller fragments, which when they accumulate, lead to Alzheimer disease. Second, carrying the same variant protects against age-related cognitive decline. Third, the Icelandic population is a remarkable group for studying genomic medicine.
From sequencing the genomes of “only” 1795 Icelanders, the investigators in this study could identify the carriers of this beneficial variant among 296,496 relatives – probably the whole population of Iceland! They could then track down those elderly people in nursing homes who retained their intellectual sharpness and carried this beneficial variant.
This is merely the tip of the genomic medicine iceberg up north.
Harry Ostrer, M.D.
Professor of Genetics, Pathology and Pediatrics Albert Einstein College of Medicine
Director, Genetic and Genomic Testing, Clinical Pathology, Montefiore Medical Center
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This is a very interesting paper with a lot of potential.
But the general public and the scientific community must keep the following in mind:
a. This is an association study (in an isolated population) so there’s no guarantee that these findings can be replicated in an independent population.
b. Despite the promising nature of these findings, the reality is it could take 15 years or longer for an effective drug to be developed that could replicate this protective effect – even if findings are proven in additional studies.
c. The gene variant is extremely rare and thus might be protective only in a highly select group of patients versus a wider population.
In sum, clues from this study show potential but we must sound the cautionary note that, scientifically, it is premature to call this a breakthrough for patients.
Gil Atzmon, Ph.D.
Associate Professor of Medicine, Albert Einstein College of Medicine
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Scientists have long been searching for genes that cause certain diseases, with mixed success, as in the case of Alzheimer’s diseases (AD). Rather than a variant, or mutation, in a gene that may cause a disease, this paper reports a variant that protects against AD. This mutation is in a pathway that scientists have hypothesized to be relevant to the cause of AD, and a strategy to develop a treatment has now been adopted by pharmaceutical companies.
Interestingly in studies at Einstein, including the Longevity Genes Study, we have been focused for over a decade on identifying protective genes against aging and its related diseases. We also have discovered a variant in a gene (cholesterol ester transfer protein or CETP) that protects against several age-related diseases including AD in our study group, the families of centenarians. CETP is also a target for drug development.
Thus, identifying and seeking to duplicate protective genetic factors may become a mainstream approach to curing or preventing diseases.
Nir Barzilai, M.D.
Director, Institute for Aging Research, Albert Einstein College of Medicine
Attending Physician, Medicine (Endocrinology), Montefiore Medical Center
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