Neurogranin Could Predict Progression to Alzheimer's

Elevated levels of a postsynaptic protein called neurogranin may be predictive of progression from mild cognitive impairment to Alzheimer’s disease.

Researchers from the VU University Medical Center in Amsterdam, the Netherlands and the Washington University School of Medicine in St. Louis, Mo., showed that neurogranin levels were higher in patients with Alzheimer’s disease compared with cognitively normal study participants. In addition, those with mild cognitive impairment that progressed to Alzheimer’s had higher levels of neurogranin compared to those with stable impairment. The study is published in the September 14 issue of JAMA Neurology.

Maartje I. Kester, MD, PhD, and colleagues, followed patients from the Amsterdam Dementia Cohort for up to four years. The study group included 65 patients with Alzheimer’s disease, 61 patients with mild cognitive impairment, and 37 patients who were cognitively normal, although some from the last group did experience some memory complaints.

All patients underwent standard dementia screening, cognitive screening, and comprehensive neuropsychological testing. They gave two cerebrospinal fluid samples, which were tested for neurogranin levels at regular intervals.

“[Neurogranin] levels are lower in the cognitively normal participants than in patients with [Alzheimer’s disease], and then they increase over time,” the authors wrote.

Currently used biomarkers (Aβ42, total tau, and tau phosphorylated at threonine 181) indicate amyloid plaques and neurofibrillary tangles that characterize Alzheimer’s disease. However, because these biomarkers remain stable, they do not indicate further decline once symptoms of cognitive impairment become apparent.

“[T]he neurogranin level could have added value because it is a reflection of a pathophysiological process that is directly related to cognitive changes,” the authors wrote. Loss of synapses begins early in the progression of Alzheimer’s disease and is an indicator of cognitive decline. “Biomarkers that reflect synaptic integrity could therefore be useful for both an accurate, early diagnosis and disease prognosis,” they noted.