In the search for better diagnostic tests for Alzheimer’s, researchers may soon develop a test measuring proteins in cerebrospinal fluid predictive of the mental decline that characterizes the degenerative disease.
Science has long searched for biomarkers to help identify early stages of the disease years ahead of memory loss and other symptoms. Improved diagnostic tools would potentially allow doctors to prescribe drugs that may slow or prevent the progression of the disease while patients still maintain their cognitive functioning.
However, such treatments remain distant as medications intended to stop brain damage caused by Alzheimer’s have failed in numerous clinical trials. But those treatments may work sooner in the disease progression, researchers believe.
"When we see patients with high blood pressure and high cholesterol, we don't say we will wait to treat you until you get congestive heart failure. Early treatments keep heart disease patients from getting worse, and it's possible the same may be true for those with pre-symptomatic Alzheimer's," Marilyn Albert, a neurologist at the Johns Hopkins University School of Medicine, who led the study, published Wednesday. "But it has been hard to see Alzheimer's disease coming, even though we believe it begins developing in the brain a decade or more before the onset of symptoms," she said.
In the study, Albert and her colleagues used cerebrospinal fluid collected from healthy participants in a study of dementia risk between 1995 and 2005. Among that study group, approximately three-quarters reported a close family member with Alzheimer’s disease, indicating a higher than average risk for developing the disorder. During those years of the study and again beginning in 2009, researchers tested those participants with a battery of neuropsychological tests and a physical exam.
In a breakthrough, they found that specific baseline ratios of two proteins—phosphorylated tau and beta amyloid, found in cerebrospinal fluid—presaged the mild cognitive impairment characterizing an early stage of the disorder occurring five or so years before the onset of Alzheimer’s symptoms. Participants with higher levels of the two proteins, and those with levels quickly rising, were more likely to develop symptoms of the disorder.
Although researchers had previously known of the association between these proteins and patients with advanced Alzheimer’s, the study confirmed the biomarker as useful for testing during early stages prior to cognitive decline. “We wondered if we could measure something in the cerebral spinal fluid when people are cognitively normal to give us some idea of when they will develop difficulty," Albert said. "The answer is yes."
The researchers believe that small amounts of beta-amyloid in the spinal fluid decreases as the disease progresses, getting trapped in amyloid plaques that develop when neurons stop working, lose synaptic connections with other cells, and die. In the brains of those with advanced stages of Alzheimer’s, these plaques are found along with “tangles” comprised of tau.
However, the biomarker test is not yet sophisticated enough to accurately predict one’s chances of developing Alzheimer’s, with further study needed.
Source: Moghekar, Abhay, Li, Shanshan, Lu, Yi, Li, Ming, Wang, Mei-Cheng, O'Brien, Richard. CSF Biomarker Changes Precede Symptom Onset Of Mild Cognitive Impairment. Neurology. 2013.