Locating genes for clues to Alzheimer's risk, cause, diagnosis

Neuroscientists have zeroed in on some target genes that may be tied to the development of Alzheimer's disease, and they've shown what abnormalities appear on brain scans of people with these genetic variations.

Both bits of scientific progress are incremental steps toward understanding what causes the disease that afflicts more than 5 millon Americans. The study, lead by researchers in Boston and Cambridge, Mass., England and Wales, appears in this month's Archives of Neurology.

"The drought of genetic findings in Alzheimer's disease has lasted a long time," write scientists based in London and Wales in an editorial accompanying the Archives study. "These findings, and the genome-wide studies that presaged them, mark a new period of optimism for those of us who study the etiologies of complex diseases of the nervous system."

The study explains the association researchers made between genetic loci that are related to Alzheimer's disease and neuorimaging measures that are related to disease risk. (These measures include the volume of the hippocampus, amygdala and other brain structures.) They identify B1N1 and CNTN5 as additional specific locations of genetic variants on chromosomes, but say their findings warrant further study.

Just one genetic variant, known as APOE, has been shown to influence Alzheiemer's disease risk and age at onset, lead authors Drs. Alessandro Biffi and Christopher Anderson write in their background information.

Study participants included 168 people with probable Alzheimer's, 357 people with mild cognitive impairment, a precursor to Alzheimer's, and 215 people who were cognitively normal. "Our results indicate that APOE and other previously validated loci for Alzheimer's disease affect clinical diagnosis of Alzheimer's disease and neuroimaging measures associated with the disease," they write.

Will that bring us closer to genetic tests for Alzheimer's?

Somewhat, John Hardy, of the University College London Institute of Neurology, says in an email, "but I think this genetic determinism argument is oversold, frankly.

"About 5 percent of the population are at high risk. About 30 percent of the population are at a moderate risk, and about 65 percent are at lower risk. These numbers are little changed by the new data. And, this is not really so useful for genetic testing."

Read the study in the Archives of Neurology.

The National Institute on Aging's fact sheet on Alzheimer's disease genetics.

If there were a test for dementia, would you take it?

Especially if Alzheimer's disease "runs in the family," we listen when scientists talk of ways to predict who will develop such a dreadful disease. We've heard more about the brain than we care to, with its tau proteins and plaques and neurofibrillary tangles. Of course brain research is teaching us about the causes of dementia, and maybe it will eventually lead to methods of prevention or treatment. Will those advances come in time for us? For our children?

Earlier this year, research in the Neurobiology of Aging Journal explained how elevated levels of phosphorylated tau231 in cerebrospinal fluid may be used to diagnose a healthy person who will develop Alzheimer's disease. Researchers from New York University's School of Medicine said the levels could predict future memory decline and the loss of brain gray matter in the medial temporal lobe--a key memory center.

"Our research results show for the first time that elevated levels of P-tau 231 in normal individuals can predict memory decline and accompanying brain atrophy," said lead author Dr. Lidia Glodzik, an assistant research professor in the Department of Psychiatry at the school's Center for Brain Health and Center of Excellence on Brain Aging. "Our findings suggest that P-tau231 has the potential to be an important diagnostic tool in the pre-symptomatic stages of Alzheimer's disease."

Which is great.

Or at least, potentially, a great advance.

It's quite a ways off. When I go for my physical in a couple of weeks, I won't be able to ask my doctor to run this test and then...know. But there's a good chance something like this will be available if not in my lifetime, certainly within the lifetimes of my children.

We know what Alzheimer's and dementia do to the ones we love. We know how the diseases take them from us long before their bodies fail, leaving bits of their spirit and personality glimmering--only every now and then--in their eyes. One merciful aspect of the disease may be that our loved ones did NOT know what was happening to them until it already was. By the time symptoms of memory failure became evident, hopefully, they were too far gone to notice. What appears to us as suffering may be, to them, just the way life is.

Science may wind up changing that for us.

We may have the option of learning way before symptoms emerge whether dementia is part of our future. So, what if it is? What then?

Read the story in ScienceDaily.

Read the story in The Medical News.

The abstract in the Neurobiology of Aging.

Genetic clue may help explain FTD risk

A gene on chromosome 7 may increase a person's risk of developing frontotemporal lobe dementia, according to an international team of scientists writing in the journal, Nature Genetics. Their work compared the brains of 515 individuals with FTD with the brains of 2,509 healthy people.

"We found a specific genetic change that was associated with an increased risk of the disease," co-author Maria Grazia Spillantini, of the University of Cambridge, told the Telegraph. “A better understanding of how the gene is involved could identify a new approach to tackle this disease.”

The paper lists FTD as the second most common cause of presenile dementia, which is dementia occuring in people younger than age 65.

The BBC story.

The Telegraph story.

Read the journal abstract (to read the article incurs a fee.)