Biomarkers may predict progression to Alzheimer's

NEW YORK (Reuters Health) - Swedish doctors have evidence that concentrations of three proteins in the fluid that bathes the brain and spine are associated with the initial stages of Alzheimer's disease in people with mild cognitive impairment.

Although mild cognitive impairment is a risk factor for Alzheimer's disease, the condition can also be relatively stable, Dr. Kaj Blennow, from Sahlgrenska University Hospital in Goteborg and colleagues explain in The Lancet Neurology.

They measured levels of three proteins related to Alzheimer's disease -- AB42, T-tau, and P-tau181 -- in CSF samples from 137 patients with mild cognitive impairment and 39 controls.

During 4 to 6 years of follow-up, 56 of the subjects with mild cognitive impairment remained cognitively stable, 3 died, 57 developed Alzheimer's disease, and 21 progressed to other forms of dementia.

According to the investigators, baseline concentrations of T-tau and P-tau181 were significantly higher, and AB42 significantly lower, among patients who developed Alzheimer's disease compared with controls, cognitively stable patients with mild cognitive impairment, and patients who developed other forms of dementia.

Using certain cutoff levels, these proteins were 95 percent sensitive and 87 percent specific for progression to Alzheimer's disease in patients with mild cognitive impairment.

These findings, the authors state, indicate that "molecular changes that can be measured in CSF are probably well underway when the earliest symptoms of Alzheimer's disease become clinically manifest."

They add: "If validated in other consecutive studies with long follow-up, these results may have an effect both on the diagnostic work-up and on the design of clinical trials of patients with mild cognitive impairment."

SOURCE: Lancet Neurology, online February 6, 2006.