"Reliability and failure to replicate initial results have been the biggest challenge in this field," says lead author William Hu.
Hu and his collaborators at the University of Pennsylvania and Washington University, measured the levels of 190 proteins in the blood of 600 study participants at those institutions.
Study participants included healthy volunteers and those who had been diagnosed with Alzheimer's disease (AD) or mild cognitive impairment (MCI).
MCI, often considered a harbinger for Alzheimer's disease, causes a slight but measurable decline in cognitive abilities.
A subset of the 190 protein levels (17) were significantly different in people with MCI or Alzheimer's.
When those markers were checked against data from 566 people participating in the multicenter Alzheimer's Disease Neuroimaging Initiative, only four markers remained.
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"We were looking for a sensitive signal," says Hu.
"MCI has been hypothesised to be an early phase of AD, and sensitive markers that capture the physiological changes in both MCI and AD would be most helpful clinically," he said.
Neurologists currently diagnose Alzheimer's disease based mainly on clinical symptoms. Additional information can come from PET brain imaging, which tends to be expensive, or analysis of a spinal tap, which can be painful.
"Though a blood test to identify underlying Alzheimer's disease is not quite ready for prime time given today's technology, we now have identified ways to make sure that a test will be reliable," says Hu.
The possibility of an inexpensive, convenient test for Alzheimer's disease has been on the horizon for several years, but previous research leads have been hard to duplicate.