Cerebral amyloid load determination in a clinical setting: interpretation of amyloid biomarker discordances aided by tau and neurodegeneration measurements

Background Alzheimer's disease (AD) diagnosis can be hindered by amyloid biomarkers discordances. Objective We aim to interpret discordances between amyloid positron emission tomography (Amy-PET) and cerebrospinal fluid (CSF) (A beta(42) and A beta(42/40)), using Amy-PET semiquantitative analysis, [F-18]fluorodeoxyglucose (FDG)-PET pattern, and CSF assays. Method Thirty-six subjects with dementia or mild cognitive impairment, assessed by neuropsychological tests, structural and functional imaging, and CSF assays (A beta(42), A beta(42/40), p-tau, t-tau), were retrospectively examined. Amy-PET and FDG-PET scans were analyzed by visual assessment and voxel-based analysis. SUVR were calculated on Amy-PET scans. Results Groups were defined basing on the agreement among CSF A beta(42) (A), CSF A beta(42/40) Ratio (R), and Amy-PET (P) dichotomic results ( +/-). In discordant groups, CSF assays, Amy-PET semiquantification, and FDG-PET patterns supported the diagnosis suggested by any two agreeing amyloid biomarkers. In groups with discordant CSF A beta(42), the ratio always agrees with Amy-PET results, solving both false-negative and false-positive A beta(42) results, with A beta(42) levels close to the cut-off in A + R-P- subjects. The A + R + P- group presented high amyloid deposition in relevant areas, such as precuneus, posterior cingulate cortex (PCC) and dorsolateral frontal inferior cortex at semiquantitative analysis. Conclusion The amyloid discordant cases could be overcome by combining CSF A beta(42), CSF ratio, and Amy-PET results. The concordance of any 2 out of the 3 biomarkers seems to reveal the remaining one as a false result. A cut-off point review could avoid CSF A beta(42) false-negative results. The regional semiquantitative Amy-PET analysis in AD areas, such as precuneus and PCC, could increase the accuracy in AD diagnosis.

Automated summary

The study aims to interpret discrepancies between amyloid PET and CSF biomarkers in Alzheimer's disease diagnosis, utilizing a combination of different imaging and biomarker analysis techniques to improve diagnostic accuracy.