CSF Neurogranin or Tau Distinguish Typical and Atypical Alzheimer Disease

Objective: To assess whether high levels of cerebrospinal fluid neurogranin are found in atypical as well as typical Alzheimer's disease.

Methods: Immunoassays were used to measure cerebrospinal fluid neurogranin in 114 participants including healthy controls ( = 27), biomarker-proven amnestic Alzheimer's disease ( = 68), and the atypical visual variant of Alzheimer's ( = 19) according to international criteria. CSF total-tau, Aβ42, and neurofilament light concentrations were investigated using commercially available assays. All affected individuals had T1-weighted volumetric MR images available for analysis of whole and regional brain volumes. Associations between neurogranin, brain volumes, total-tau, Aβ42, and neurofilament light were assessed.

Results: Median cerebrospinal fluid neurogranin concentrations were higher in typical and atypical Alzheimer's compared to controls ( < 0.001 and  = 0.005). Both neurogranin and total-tau concentrations, but not neurofilament light and Aβ42, were higher in typical Alzheimer's compared to atypical patients ( = 0.004 and  = 0.03). There were significant differences in the left hippocampus and right and left superior parietal lobules in atypical patients, which were larger ( = 0.03) and smaller ( = 0.001 and  < 0.001), respectively, compared to typical patients. We found no evidence of associations between neurogranin and brain volumes but a strong association with total-tau ( < 0.001) and a weaker association with neurofilament light ( = 0.005).

Interpretation: These results show significant differences in neurogranin and total-tau between typical and atypical patients, which may relate to factors other than disease topography. The differential relationships between neurogranin, total-tau and neurofilament light in the Alzheimer's variants, provide evidence for mechanistically distinct and coupled markers of neurodegeneration.