Report from the 1st Congress of the European Academy of Neurology, Berlin, Germany, June 20-23, 2015 – Imaging and CSF biomarkers of neurodegeneration appear to be correlated only in patients with Alzheimer’s disease with beta-amyloid pathology, according to a study by the Alzheimer’s Disease Neuroimaging Initiative (Andriutal et al. EAN 2015;O3102).
CSF and cerebral 18-fluorodeoxyglucose (FDG)-positron emission tomography (PET) results were compared for 75 AD patients, 215 patients with mild cognitive impairment and 82 normal controls. Cerebral hypometabolism on FDG-PET and the CSF markers total tau (t-tau) and hyperphosphorylated tau (p-tau) were significantly correlated only in patients with abnormal CSF beta-amyloid1-42. Among patients with beta-amyloid pathology, CSF p-tau was the marker that was most commonly abnormal.
Full results of the study have been recently published and included an analysis of the temporal relationship between neuroimaging, CSF and cognitive changes (Dowling et al. Neuroimage 2015;105:357-368). The authors hypothesized that abnormal CSF proteins result in decreased neuronal glucose metabolism in selected brain regions. Of particular interest is the middle/inferior temporal gyrus, where beta-amyloid1-42 has been shown to have a direct effect on hypometabolism.
Comment:
Dr. Catherine Brodeur: Two general types of biomarkers are present in Alzheimer’s pathology: biomarkers of brain Aβ amyloidosis and biomarkers of synaptic dysfunction. The first type includes reductions in CSF beta-amyloid42 and increased amyloid tracer retention on PET imaging. The second type includes markers of neuronal injury: elevated CSF tau or p-tau, decreased FDG uptake on PET scan with a temporoparietal pattern, and cortical thinning/gray matter loss in a specific anatomic distribution. The studies mentioned above corroborate the hypothesis that beta-amyloid accumulation is sufficient to incite the downstream pathological cascade of AD.