Neurology Today Conference Reporter: Alzheimer’s Association International Conference

Access timely, concise peer-reviewed reports from the Alzheimer’s Association International Conference selected by the Neurology Today editors.

Tuesday, July 21, 2015

July 21—Neurogranin, a CSF Biomarker for Synaptic Loss, Is Found to Predict Progression from MCI to Alzheimer’s Disease

BY REBECCA HISCOTT

 

WASHINGTON—Levels of neurogranin, a cerebrospinal fluid (CSF) biomarker for synaptic loss, were elevated in patients with Alzheimer’s disease (AD) compared with cognitively normal individuals. Neurogranin levels also predicted progression from mild cognitive impairment (MCI) to AD dementia, researchers reported here on Monday at the Alzheimer’s Association International Conference (AAIC).

 

“In Alzheimer’s disease, synaptic loss is an early pathologic event and is correlated to cognitive decline. With this study we hoped to find a biomarker that reflects early Alzheimer’s disease and correlates with disease progression,” study author Maartje Kester, MD, PhD, of the department of neurology and the Alzheimer Center at VU University Medical Center in Amsterdam, the Netherlands, told the Neurology Today Conference Reporter ahead of the session.

 

Charlotte Teunissen, PhD, an assistant professor in the department of clinical chemistry at VU University Medical Center, presented the findings on behalf of Dr. Kester at the AAIC.

 

The researchers measured CSF levels of neurogranin in 37 cognitively normal individuals with a mean age of 64, 61 people with MCI with a mean age of 68, and 65 patients with AD with a mean age of 65. The patients were enrolled in the Amsterdam Dementia Cohort and received two lumbar punctures two years apart. They were followed for approximately 3.8 years.

 

Among the findings, baseline levels of neurogranin were higher in AD patients than in cognitively normal individuals (p=0.04) and were strongly correlated with levels of tau and phosphorylated tau (p<0.001), but not amyloid-beta. People with MCI who progressed to AD had higher baseline levels of neurogranin than those with stable MCI that did not progress to AD during the study period (p=0.004). Neurogranin levels were predictive of progression from MCI to AD (hazard ratio [HR] 1.8; 95% confidence interval [CI], 1.1-2.9; tertiles), the researchers reported.

 

Based on the findings, neurogranin “could have a future role in the diagnostic process, probably in combination with the core CSF biomarkers [amyloid and tau],” Dr. Kester said. “Furthermore, it could have a role in the monitoring of disease progression in treatment trials.”

 

She added, “We hope that our study will be replicated in other cohorts. In addition, studies on associations between this novel CSF biomarker and other functional measures, like repeated neuropsychological examination or EEG, are needed to further understanding of neurogranin in the pathogenesis of AD.”

 

Commenting on the findings, Stephen T. DeKosky, MD, FAAN, deputy director of the McKnight Brain Institute and a professor of neurology in the University of Florida College of Medicine, said it’s unclear what neurogranin adds to the existing, validated CSF biomarkers for progression from MCI to AD.

 

“If you’re going to do a spinal tap and you’re looking for signs of Alzheimer’s disease, you’re going to run screens for tau, phosphorylated tau, and amyloid-beta. We already have good data on their predictability,” he said. “If you look at people who have MCI and they have low amyloid and high tau, we already know that 90 percent of them are probably going to get AD within five years. So how much more neurogranin adds to that, I don’t know.”

 

However, he added, “I think neurogranin can be useful to tell us something more about the pathology of the disease. It’s a solid marker, statistically, that synapses are being lost in the course of the disease, even without manifest evidence of cognitive loss. So I see it more as a marker for helping us understand the timing of the pathology, rather than a diagnostic marker. These data may teach us about the nature and timing of synaptic degeneration.”

 

LINK UP FOR MORE INFORMATION:

 

·         Amsterdam Dementia Cohort: http://bit.ly/Amsterdam-dementia