Finding Alzheimer’s Disease before symptoms start

Johns Hopkins researchers say that by measuring levels of certain proteins in cerebrospinal fluid (CSF), they can predict when people will develop the cognitive impairment associated with Alzheimer’s disease years before the first symptoms of memory loss appear.
Identifying such biomarkers could provide a long-sought tool to guide earlier use of potential drug treatments to prevent or halt the progression of Alzheimer’s while people are still cognitively normal.
To date, medications designed to stop the brain damage have failed in clinical trials, possibly, many researchers say, because they are given to those who already have symptoms and too much damage to overcome.
‘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,’ says Marilyn Albert, Ph.D., a professor of neurology at the Johns Hopkins University School of Medicine. ‘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 adds.
For the new study, the Hopkins team used CSF collected for the Biomarkers for Older Controls at Risk for Dementia (BIOCARD) project between 1995 and 2005, from 265 middle-aged healthy volunteers. Some three-quarters of the group had a close family member with Alzheimer’s disease, a factor putting them at higher than normal risk of developing the disorder. Annually during those years and again beginning in 2009, researchers gave the subjects a battery of neuropsychological tests and a physical exam.
They found that particular baseline ratios of two proteins — phosphorylated tau and beta amyloid found in CSF — were a harbinger of mild cognitive impairment (often a precursor to Alzheimer’s) more than five years before symptom onset. They also found that the rate of change over time in the ratio was also predictive. The more tau and the less beta amyloid found in the spinal fluid, the more likely the development of symptoms. And, Albert says, the more rapidly the ratio of tau to beta amyloid goes up, the more likely the eventual development of symptoms.
Researchers have known that these proteins were in the spinal fluid of patients with advanced disease. ‘But 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 says. ‘The answer is yes.’ John Hopkins Medicine