Biomarker Predicts Dementia-Related Decline Caused by Alzheimer’s Disease

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Researchers identify significantly higher levels of neurogranin in patients with Alzheimer's disease versus cognitively normal patients.

WASHINGTON — Compared with cognitively normal individuals, those with Alzheimer’s disease have been found to have increased levels of neurogranin, a novel cerebrospinal fluid (CSF) biomarker of synaptic loss, according to new data.

“We found that neurogranin is a potentially useful marker for the diagnosis, prognosis, and monitoring of Alzheimer’s,” study investigator Maartje Kester, MD, PhD, of VU University Medical Center in Amsterdam, said in a statement.

Kester and colleagues reported the findings at the Alzheimer’s Association International Conference.

For the study, researchers measured CSF levels of neurogranin in 163 patients: 37 who were cognitively normal; 61 who had mild cognitive impairment (MCI); and 65 who had Alzheimer’s disease. All patients were from the Amsterdam Dementia Cohort and underwent two lumbar punctures (mean interval, 2 years) to allow researchers to compare protein content.

Cognitive exams were also performed approximately 4 years apart to show how patients’ memory and thinking status changed over time.

Researchers adjusted for sex and age, and used analysis of variance (ANOVA) to determine baseline differences and Cox regression analysis to predict the progression to Alzheimer’s disease in patients with MCI.

Mean cognitive follow-up was 3.8 years.

Results indicated that baseline levels of neurogranin were significantly higher in patients with Alzheimer’s disease than in cognitively normal individuals (P=.04), and correlated with tau and ptau-181 in all groups (P<.001) except amyloid beta 42.

In addition, baseline neurogranin levels were increased in patients with MCI that progressed to Alzheimer’s disease vs those with stable MCI (P=.004), and predicted the progression from MCI to Alzheimer’s disease (HR=1.8; 95% CI, 1.1-2.9).

In linear mixed model analyses, which were used to determine within-person annual change in neurogranin levels, neurogranin levels increased in the cognitively normal group (mean, 90 pg/mL per year; P<.05), but not in those with MCI or Alzheimer’s disease.

“This may indicate that neurogranin levels in CSF reflect very early synaptic loss in Alzheimer’s and may be useful for early detection,” Kester said.


Kester M, et al. Abstract #4301. Neurogranin, a CSF biomarker for synaptic loss, predicts decline to dementia due to Alzheimer’s disease.Presented at: Alzheimer’s Association International Conference 2015: July 18-23, 2015; Washington, D.C.