Results of a long-term, federally funded study of cognitively healthy adults — most with a family history of Alzheimer’s disease — have added to evidence that low spinal fluid levels of a protein linked to learning and memory in mice may serve as an early predictor of mild cognitive impairment (MCI) years before symptoms appear.

The findings, which may potentially offer new targets for treating or preventing Alzheimer’s and other dementias, showed that a relatively low level of the protein known as NPTX2 is not only a likely standalone risk factor for MCI and Alzheimer’s dementia but also improves prediction of cognitive impairment after accounting for levels of traditional biomarkers and well-established genetic risk factors for Alzheimer’s.

The study, conducted by Johns Hopkins Medicine scientists on more than 250 primarily middle-aged adults, the vast majority of whom were white, concluded that the findings were consistent with and expand prior studies by establishing that measurements of NPTX2 in cerebrospinal fluid were predictive of MCI onset within or even beyond seven years before symptoms occurred.

A report on the study was published July 25 in Annals of Neurology.

The growing prevalence of dementias has given urgency to the search for better and earlier predictors, and targets for treatments that prevent or slow progression. At present, there is only one FDA-approved drug on the market known to even modestly slow symptoms of Alzheimer’s in its early stages, and there are no cures or preventives.

“Our research shows declining levels of NPTX2 occur many years prior to the emergence of MCI or Alzheimer’s symptoms, which raises the possibility of developing new therapeutics that target NPTX2,” says neurologist Anja Soldan, corresponding author of the study.

“Additionally, it appears that this protein is not a specific marker to just Alzheimer’s, and these findings may be relevant to a variety of other neurodegenerative diseases. So if we can find ways of increasing levels of NPTX2, then it could be applied to identify early and possibly treat other types of memory loss or cognitive impairment as well.”