Abbreviated MTHFD1L, a gene which is located in chromosome six has been linked to a higher risk of developing late-onset Alzheimer’s disease. 90% of cases of Alzheimer’s disease are late-onset, which affect individuals over the age of 65 years, hence the name. MTHFD1L was detected in a genome-wide association study led by led by Margaret Pericak-Vance, Ph.D., director of the John P. Hussman Institute for Human Genomics (HIHG) at the University of Miami Miller School of Medicine and team.

You can read about this study in PLoS Genetics, September 23rd issue.

According to WHO (World Health Organization), approximately 18 million people have Alzheimer’s disease worldwide; the figure is expected to reach 34 million within the next 20 years.

As background information, the authors explain that Alzheimer’s disease is a neurodegenerative disorder with memory and cognitive impairment. It affects over 13% of people aged at least 65 years. It is the most common type of dementia among seniors.

The investigators examined the human genomes of 2,269 patients with late-onset Alzheimer’s disease, as well as 3,107 healthy individuals. There were able to identify small variations in the genetic sequences of those with and without AD (Alzheimer’s disease).

People with MTHFD1L, a particular variation in the gene, were found to have nearly twice the risk of developing late-onset AD compared to those without the variation, the authors report.

Author Adam Naj, Ph.D. wrote:

We are hopeful our identification of MTHFD1L as a risk gene for Alzheimer’s disease will help us to better understand how this disease develops and potentially serve as a marker for people who may be at increased risk.

Dr. Pericak-Vance, said:

Identifying this gene is important because the gene is known to be involved in influencing the body’s levels of homocysteine, and high levels of homocysteine are a strong risk factor for late-onset Alzheimer’s disease. In addition, variations of the MTHFD1L gene have been reported to possibly increase the risk of coronary artery disease. Since the function of blood vessels in the brain may affect Alzheimer’s disease, this finding may also help us understand how homocysteine levels and blood vessel function in the brain affect Alzheimer’s disease.

Jonathan Haines, Ph.D., Principal Investigator at Vanderbilt University School of Medicine, said:

By applying the new tools of genomics we are now making rapid progress in finding out what genetic changes are involved in Alzheimer disease. These findings will lead to a better understanding of what’s happening in Alzheimer disease, and how we can improve treatments.

Co-author, Joseph Buxbaum, Ph.D., from Mount Sinai School of Medicine in New York, wrote:

This finding gives us unique insight into possible interactions between genetic and environmental risk factors that contribute to AD. We know of environmental and lifestyle factors that can impact homocysteine levels and it will be important to understand whether variations of the MTHFD1L gene can modulate these effects.

Alzheimer’s disease is a progressive neurologic disease of the brain leading to the irreversible loss of neurons and the loss of intellectual abilities, including memory and reasoning, which become severe enough to impede social or occupational functioning. The disease is also known as simply Alzheimer’s, and Senile Dementia of the Alzheimer Type (SDAT).

During the course of the disease plaques and tangles develop within the structure of the brain. This causes brain cells to die. Patients with Alzheimer’s also have a deficiency in the levels of some vital brain chemicals which are involved with the transmission of messages in the brain – neurotransmitters.

Alzheimer’s disease is the most common form of dementia. The disease gets worse as it develops, hence the description, aprogressive disease. There is no current cure for Alzheimer’s, although there are ways of slowing down its advance and helping patients with some of the symptoms. Alzheimer’s is also a terminal disease – it is incurable and causes death.

The main reason Alzheimer’s disease shortens people’s life expectancy is not usually the disease itself, but complications that result from it. As patients become less able to look after themselves, any illnesses they develop, such as an infection, are more likely to rapidly get worse. Caregivers will find it harder and harder to identify complications because the patient becomes progressively less able to tell if he/she is unwell, uncomfortable, or in pain. Pneumonia and pressure ulcers are examples of common complications which may lead to death for people with severe Alzheimer’s disease.

A doctor can diagnose most cases of Alzheimer’s. The physician will usually attempt to rule out other conditions which may sometimes present similar symptoms, such as anxiety, a brain tumor, depression, infection, thyroid problems, or vitamin deficiency. However, nobody can be 100% sure until after death, when a microscopic examination of the brain detects plaques and tangles. There is no basic testing, such as a blood test, urine test, biopsy, or image scan for diagnosing Alzheimer’s disease. A brain scan may help identify changes in the brain.

Click here to read about Alzheimer’s disease in more detail.

“Dementia Revealed: Novel Chromosome 6 Locus for Late-Onset Alzheimer Disease Provides Genetic Evidence for Folate-Pathway Abnormalities”
Adam C. Naj, Gary W. Beecham, Eden R. Martin, Paul J. Gallins, Eric H. Powell, Ioanna Konidari, Patrice L. Whitehead, Guiqing Cai, Vahram Haroutunian, William K. Scott, Jeffery M. Vance, Michael A. Slifer, Harry E. Gwirtsman, John R. Gilbert, Jonathan L. Haines., Joseph D. Buxbaum, Margaret A. Pericak-Vance1
PLoS Genet 6(9): e1001130. doi:10.1371/journal.pgen.1001130

Written by Christian Nordqvist