Mild cognitive impairment is predicted by low protein levels in spinal fluid: Study
Washington DC, US: The amount of a protein linked to learning and memory in mice found in the spinal fluid may act as an early predictor of mild cognitive impairment (MCI) years before symptoms appear, according to a study of cognitively healthy adults.
The results demonstrate that a low level of the protein NPTX2 is not only a likely standalone risk factor for MCI and Alzheimer's dementia but also improves the prediction of cognitive impairment after controlling for levels of conventional biomarkers and well-established genetic risk factors for Alzheimer's.
These findings could lead to new targets for treating or preventing Alzheimer's and other dementias.
Researchers from Johns Hopkins Medicine found that measurements of NPTX2 in cerebrospinal fluid were predictive of MCI onset within or even beyond seven years prior to the onset of symptoms in more than 250 primarily middle-aged adults, the vast majority of whom were white.
The Annals of Neurology published the study's findings.
Up to 18% of people aged 60 and older experience MCI, which is characterised by mild memory loss or difficulties with other cognitive functions like language or executive function.
The majority of their daily routines are maintained by people with MCI, despite the fact that they are more likely to develop dementia, including Alzheimer's disease.
By 2050, it is anticipated that there will be 6.7 million Americans aged 65 and older who are living with Alzheimer's dementia. The need for more accurate and earlier predictors, as well as targets for treatments that can stop or slow progression, has increased due to the increasing prevalence of dementias.
There are currently neither treatments nor preventives for Alzheimer's disease; rather, the only FDA-approved medication on the market is known to only slightly slow the disease's early-stage symptoms.
“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 Anja Soldan, PhD, associate professor of neurology at the Johns Hopkins University School of Medicine and 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.”
For the study, which involved adults recruited by the National Institutes of Health and Johns Hopkins Medicine, researchers conducted baseline medical and cognitive exams on 269 cognitively normal individuals and collected spinal fluid samples biannually.
The average age of participants at baseline was 57.7 years. NPTX2 levels were measured, as well as the main abnormal proteins found in patients with Alzheimer’s, namely beta-amyloid, total tau and phosphor-tau. Subjects underwent clinical and cognitive assessments for an average of 16 years.
Results showed that over time, 77 subjects progressed to MCI or dementia within or after seven years of baseline measurements.
Those who progressed to MCI had on average about 15 per cent lower levels of NPTX2 at baseline compared with those who remained unimpaired, a difference that remained significant after accounting for baseline Alzheimer’s biomarker levels and genetic factors.
Higher levels of baseline tau and phosphor-tau levels were associated with greater decreases in NPTX2 over time, suggesting that NPTX2 may decline in response to tau pathology.
“Currently, we only have drugs that modify mild symptoms of Alzheimer’s disease and nothing right now to give people who are cognitively normal but at higher risk,” Soldan emphasized. But when and if that changes, Soldan adds, having an accurate way to predict such risk will play a large role in targeting treatments.
