Spinal Fluid Biomarkers Predict Cognitive Decline in Individuals with Familial Risk of Alzheimer's Disease

Determination of two biomarkers in cerebrospinal fluid (CSF) allows prediction of development of cognitive impairment up to five years before appearance of symptoms in normal patients with familial risk of Alzheimer's disease.

Investigators at Johns Hopkins University (Baltimore, MD, USA) measured beta-amyloid 1–42 (Abeta1–42), total tau (t-tau), and phosphorylated tau (p-tau) proteins in CSF collected for the Biomarkers for Older Controls at Risk for Dementia (BIOCARD) project between 1995 and 2005, from 265 middle-aged healthy volunteers. Approximately three-quarters of this group had a close family member with Alzheimer’s disease, an indication of higher than normal risk of developing the disorder. Biochemical measurements and assessment of cognitive ability were repeated at yearly intervals.

Results revealed that the mean time from baseline to onset of mild cognitive symptoms was 5.41 years. This decline in cognitive ability was paralleled by increase in the levels of phosphorylated tau and beta amyloid found in CSF. The rate of change over time in the ratio of phosphorylated tau protein to beta amyloid was also predictive, with elevated p-tau indicating increased likelihood of development of cognitive symptoms.

“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,” said contributing author Dr. Marilyn Albert, professor of neurology at Johns Hopkins University. “The answer is yes.”

“When we see patients with high blood pressure and high cholesterol, we do not say we will wait to treat you until you get congestive heart failure. Early treatments keep heart disease patients from getting worse, and it is possible the same may be true for those with presymptomatic Alzheimer’s. 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.”

The investigators pointed out that the biomarker ratio at this point was not accurate enough to predict precisely whether a particular individual is progressing to dementia, and further analysis of information about the group over time is needed.

The study was published in the October 16, 2013, online edition of the journal Neurology.

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