Changes in the spinal fluid in middle age may help identify people at risk of developing Alzheimer’s when they are older, giving an opportunity to treat patients before memory loss and other cognitive problems arise.
This was the conclusion of a new study from Washington University in St Louis (WUSTL), MO, published in JAMA Neurology.
Senior author Anne Fagan, a professor of neurology, says:
“It’s too early to use these biomarkers to definitively predict whether individual patients will develop Alzheimer’s disease, but we’re working toward that goal.”
Alzheimer’s disease is the most common form of dementia. The condition gradually destroys the part of the brain that controls thought, memory and language. Eventually it is no longer possible to carry on a conversation and live independently.
While younger people may develop Alzheimer’s, the symptoms usually first appear after the age of 60, and the risk increases with age.
Scientists do not know exactly what causes Alzheimer’s disease, but they suspect it has something to do with the processes that trigger the build-up of clumped and tangled proteins found in the brains of people who have died of the disease.
According to the
For their study, Prof. Fagan and colleagues used data gathered over 10 years from 169 people aged 45 to 75 who were cognitively healthy when they were enrolled.
The participants were divided into three age groups: early-middle age (45-54 years), mid-middle age (55-64) and late-middle age (65-74).
Each participant underwent at least two clinical evaluations over the study period. These included brain scans, an analysis of cerebrospinal fluid biomarkers and assessments of cognitive functioning.
The researchers were particularly interested in:
- Beta-amyloid 42: the main component of protein clumps or plaques found in the brains of people with Alzheimer’s disease
- Tau: a protein that helps stabilize long thin tubes inside cells, and levels of which increase in spinal fluid as the brain damage of Alzheimer’s disease progresses
- YKL-40: a brain-cell protein that has recently been recognized as an indicator of inflammation
- Amyloid plaques: clumps of amyloid protein in the brain that can be seen with amyloid PET scans – a hallmark of Alzheimer’s disease.
Previous studies have already linked these biomarkers to Alzheimer’s disease, but the researchers note theirs is the first to use a large data set that tracks these biomarkers over time in middle-aged people.
When they analyzed the results of the clinical evaluations, the researchers found that drops in cerebrospinal beta-amyloid 42 at age 45-54 was linked to the emergence of brain plaques later in life.
They also found that cerebrospinal levels of tau and other markers of brain-cell injury rose sharply in some participants as they reached their mid-50s to their mid-70s and YKL-40 levels rose across the age groups.
The researchers also noted that the midlife biomarker patterns appeared to be linked with future cognitive deficits and were more pronounced among participants with a known variant of the gene APOE that is linked to Alzheimer’s disease.
People who have two copies of the APOE variant have a 10-fold higher risk for Alzheimer’s than noncarriers.
While previous studies have shown that all of these biomarkers are linked to Alzheimer’s disease, this is the first to use a large data set to show that the biomarkers change over time in middle-aged individuals. Prof. Fagan explains:
“Alzheimer’s is a long-term process, and that means we have to observe people for a long time to catch glimpses of it in action.”
She and her colleagues conclude that biomarkers like the ones they observed “may be useful for targeting middle-aged, asymptomatic individuals for therapeutic trials designed to prevent cognitive decline.”
The National Institutes of Health, the Foundation for Barnes-Jewish Hospital, the Fred Simmons and Olga Mohan Fund, and Eli Lilly and Co. helped to fund the study.
Meanwhile, Medical News Today recently learned of a DNA repair mechanism that could lead to new ways to treat and prevent Alzheimer’s and other brain-wasting disorders. In the journal Science Advances, a team led by a professor from Lomonov Moscow State University in Russia, describes finding a way to fix single strand breaks in DNA that were previously considered inaccessible.