Advertisement

THE RATIO OF NEUROGRANIN/BACE1 IN CSF FACILITATES CLINICAL ASSIGNMENT OF COGNITIVE DYSFUNCTION IN MILD ALZHEIMER'S DISEASE AND DEPRESSED PATIENTS WITHOUT ALZHEIMER'S DISEASE

      Background

      Cognitive deficits are common clinical signs of depression and AD. Biomarkers may help to distinguish between early stages of AD and depression not associated with AD. Recently, cerebrospinal (CSF) levels of the synaptic proteins neurogranin and BACE1 have shown potential as progression markers for AD. Here, we analyzed CSF neurogranin, as well as CSF levels of the protein BACE1, in AD and depressed patients with and without cognitive deficits.

      Methods

      We used research prototype ELISAs for measuring neurogranin and BACE1 in CSF of mild (n=21) and moderate (n=19) AD patients and depressed patients with (n=20) or without (n=20) cognitive malfunction. We also quantified CSF levels of Aβ(1-38), Aβ(1-40), Aβ(1-42) and total-tau. Cognitive performance was tested by the CERAD test battery.

      Results

      As expected, we found significantly increased CSF levels of neurogranin and BACE1 in moderate AD patients compared to depressed patients without cognitive deficits. Neurogranin CSF levels were already significantly increased in mild AD. Interestingly, the ratio of neurogranin/BACE1 enhanced the discrimination between mild AD and depression. Moreover, the ratio also significantly distinguished between mild AD and depression with cognitive deficits. For none of the analytes, significant differences were noted between both groups of depressed patients, although we saw a trend of increased CSF levels of neurogranin, BACE1 and tau. Finally, BACE1 and neurogranin were highly correlated in all groups.

      Conclusions

      Neurogranin and BACE1 can be reliably detected in CSF of depressed and AD patients and might serve as biomarkers to facilitate clinical assignment of cognitive dysfunction. It would be valuable to assess the CSF neurogranin/BACE1 ratio in remitted formerly depressed patients via longitudinally sampling, to determine whether this ratio changes over time and correlates with clinical deterioration of cognition.