The Cytoskeletal Protein Tau is Implicated in the Pathogenesis of Alzheimer's Disease Which is Characterized by Intra-Neuronal Neurofibrillary Tangles Containing Abnormally Phosphorylated Insoluble Tau. Levels of Soluble Tau Are Elevated in the Brain, the CSF, and the Plasma of Patients with Alzheimer's Disease. to Better Understand the Causes of These Elevated Levels of Tau, We Propose a Three-Compartment Kinetic Model (Brain, CSF, and Plasma). the Model Assumes that the Synthesis of Tau Follows Zero-Order Kinetics (Uncorrelated with Compartmental Tau Levels) and that the Release, Absorption, and Clearance of Tau is Governed by First-Order Kinetics (Linearly Related to Compartmental Tau Levels). Tau that is Synthesized in the Brain Compartment Can Be Released into the Interstitial Fluid, Catabolized, or Retained in Neurofibrillary Tangles. Tau Released into the Interstitial Fluid Can Mix with the CSF and Eventually Drain to the Plasma Compartment. However, Losses of Tau in the Drainage Pathways May Be Significant. the Kinetic Model Estimates Half-Life of Tau in Each Compartment (552 H in the Brain, 9.9 H in the CSF, and 10 H in the Plasma). the Kinetic Model Predicts that an Increase in the Neuronal Tau Synthesis Rate or a Decrease in Tau Catabolism Rate Best Accounts for Observed Increases in Tau Levels in the Brain, CSF, and Plasma Found in Alzheimer's Disease. Furthermore, the Model Predicts that Increases in Brain Half-Life of Tau in Alzheimer's Disease Should Be Attributed to Decreased Tau Catabolism and Not to Increased Tau Synthesis. Most Clearance of Tau in the Neuron Occurs through Catabolism Rather Than Release to the CSF Compartment. Additional Experimental Data Would Make Ascertainment of the Model Parameters More Precise.



Second Department

Biological Sciences

Third Department

Electrical and Computer Engineering


National Science Foundation, Grant W911NF-14-2-0034

Keywords and Phrases

Alzheimer's disease; clearance; CSF levels; halflife; plasma levels; steady state kinetics; tau; turnover

International Standard Serial Number (ISSN)


Document Type

Article - Journal

Document Version

Final Version

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Creative Commons Licensing

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Publication Date

09 Nov 2022