Temporal Correlation Of Csf And Neuroimaging In The Amyloid-Tau-Neurodegeneration Model Of Alzheimer Disease

Objective To evaluate temporal correlations between CSF and neuroimaging (PET and MRI) measures of amyloid, tau, and neurodegeneration in relation to Alzheimer disease (AD) progression. Methods A total of 371 cognitively unimpaired and impaired participants enrolled in longitudinal studies of AD had both CSF (beta-amyloid [A beta](42), phosphorylated tau(181), total tau, and neurofilament light chain) and neuroimaging (Pittsburgh compound B [PiB] PET, flortaucipir PET, and structural MRI) measures. The pairwise time interval between CSF and neuroimaging measures was binned into 2-year periods. Spearman correlations identified the time bin when CSF and neuroimaging measures most strongly correlated. CSF and neuroimaging measures were then binarized as biomarker-positive or biomarker-negative using Gaussian mixture modeling. Cohen kappa coefficient identified the time bin when CSF measures best agreed with corresponding neuroimaging measures when determining amyloid, tau, and neurodegeneration biomarker positivity. Results CSF A beta(42) and PiB PET showed maximal correlation when collected within 6 years of each other (R approximate to -0.5). CSF phosphorylated tau(181) and flortaucipir PET showed maximal correlation when CSF was collected 4 to 8 years prior to PET (R approximate to 0.4). CSF neurofilament light chain and cortical thickness showed low correlation, regardless of time interval (R-avg approximate to -0.3). Similarly, CSF total tau and cortical thickness had low correlation, regardless of time interval (R-avg < -0.2). Conclusions CSF A beta(42) and PiB PET best agree when acquired in close temporal proximity, whereas CSF phosphorylated tau precedes flortaucipir PET by 4 to 8 years. CSF and neuroimaging measures of neurodegeneration have low correspondence and are not interchangeable at any time interval.