Neurogranin Shows Promise as Biomarker for Alzheimer’s

neuron synapse
neuron synapse
Patients who progressed from MCI to Alzheimer's had lower levels of neurogranin than those who remained stable.

Predicting who may develop Alzheimer’s disease could have major implications for future treatment and prevention, allowing medical professionals to target individuals at the highest risk.

Now, new research indicates that a novel cerebrospinal fluid biomarker may be able to do just that.

Researchers from VU University Medical Center in Amsterdam, the Netherlands and Washington University School of Medicine in St. Louis, Mo. studied the utility of neurogranin as a biomarker for synaptic dysfunction. In total, 163 patients from the Amsterdam Dementia Cohort were included in the longitudinal study: 37 patients with normal cognitive abilities, 61 with mild cognitive impairment, and 65 with Alzheimer’s disease. Participants underwent two lumbar punctures within a mean interval of two years and had a cognitive follow-up within a mean of 3.8 years.

Based on cerebrospinal fluid samples, baseline neurogranin levels were strongly correlated with total tau and tau phosphorylated at threonine 181 across all patient groups, but not with Aβ42. Levels of neurogranin in patients with Alzheimer’s disease were greater than in cognitively normal participants, and neurogranin levels were also higher in patients with mild cognitive impairment who progressed to Alzheimer’s disease compared to those whose mild cognitive impairment remained stable. Neurogranin levels were also predictive of progression from mild cognitive impairment to Alzheimer’s disease. Further analysis also showed that within-person levels of neurogranin increased over time in cognitively normal participants, but not in those with mild cognitive impairment or Alzheimer’s disease.

Synaptic changes are understood to mainly occur in the earliest stages of the Alzheimer’s disease process, indicating that neurogranin as a biomarker could have both prognostic and diagnostic value.

“The neurogranin level could be a more specific marker for pathological changes that lead to cognitive deterioration because it represents the more specific, and potentially earlier, process of synapse loss,” Maatje I. Kester, MD, PhD, told MedPage Today.

In an accompanying editorial, Henrik Zetterberg, MD, PhD, and Kaj Blennow, MD, PhD, commented on the need for a reliable marker like neurogranin of dendritic loss in humans. “This would be a very valuable addition to the biomarker toolbox in Alzheimer’s disease diagnostics, as well as in clinical trials of novel drug candidates against,” they wrote.

They also recommended that changes in levels of neurogranin be investigated in other neurodegenerative diseases, and suggested that studies to evaluate treatment-related changes in neurogranin levels with amyloid- and tau-targeting drugs be conducted.


  1. Kester MI et al. JAMA Neurol. 2015; doi:10.1001/jamaneurol.2015.1867.
  2. Zetterberg H, Blennow K et al. JAMA Neurol. 2015; doi:10.1001/jamaneurol.2015.2075.