Temporal Correlation of CSF and Neuroimaging in the Amyloid-Tau-Neurodegeneration Model of Alzheimer Disease. (6th July 2021)

• Record Type: Journal Article
• Authors: Boerwinkle, Anna H.; Wisch, Julie K.; Chen, Charles D.; Gordon, Brian A.; Butt, Omar H.; Schindler, Suzanne E.; Sutphen, Courtney; Flores, Shaney; Dincer, Aylin; Benzinger, Tammie L.S.; Fagan, Anne M.; Morris, John C.; Ances, Beau M.
• Is Part Of: Neurology. Volume 97:Number 1(2021)
• Publication Date: 2021-07-06
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000012123
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : 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 (β-amyloid [Aβ]42, phosphorylated tau181, 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 Aβ42 and PiB PET showed maximal correlation when collected within 6 years of each other ( R ≈ −0.5). CSF phosphorylated tau181 and flortaucipir PET showed maximal correlation when CSF was collected 4 to 8 years prior to PET ( R ≈ 0.4). CSF neurofilament light chain and cortical thickness showed low correlation, regardless of time interval ( R avg ≈ −0.3). Similarly, CSF total tau and cortical thickness had low correlation, regardless of time interval ( R avg < −0.2). Conclusions: CSF Aβ42 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.