What are the Most Frequently Impaired Markers of Neurodegeneration in ADNI Subjects?
Résumé
The aim of this study was to examine the relationship between cerebrospinal fluid (CSF) levels of biomarkers for Alzheimer's disease (AD) (A beta(1-42), t-tau, and p-tau) and (18)Fluorodeoxyglucose positron emission tomography (FDG-PET) hypometabolism in subjects from the Alzheimer's Disease Neuroimaging Initiative, and specifically to determine which index of neurodegeneration was most frequently affected. The secondary objective was to determine the most frequently hypometabolic region in patients with a CSF AD signature (abnormal A beta(1-42) and abnormal p-tau). We included the 372 subjects (85 normal subjects, 212 patients with mild cognitive impairment, and 75 patients with AD) with a CSF biomarker dosage (A beta(1-42), t-tau, and p-tau) and brain FDG-PET. The relationship between FDG-PET metabolism (in five regions of interest (ROI) known to be damaged in AD) and CSF t-tau and p-tau levels was studied as a function of CSF A beta(1-42) status. FDG-PET hypometabolism and CSF t-tau and p-tau levels were correlated only in patients with an abnormal CSF A beta(1-42) level (t-tau: R-2 = 0.044, p = 0.001; p-tau: R-2 = 0.02, p = 0.03). In the latter patients, CSF p-tau was the most frequently (p = 0.0001) abnormal neurodegeneration marker (p-tau: 92.8%; FDG-PET: 56.5%; CSF t-tau: 59.1%). Within the five ROI of FDG PET, the angular gyrus metabolism (R-2 = 0.149; p = 0.0001) was selected as the most tightly associated with CSF AD signature. The relation between CSF markers of neurodegeneration (p-tau and t-tau) and brain hypometabolism (in FDG-PET) is conditioned by presence of amyloid abnormality. This finding supports the current physiopathological model of AD. P-tau is the most frequently impaired biomarker. Using FDG PET angular gyrus hypometabolism is the most sensitive to CSF-biomarker-defined AD.