Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility

Abstract

Well-authenticated biomarkers can provide critical insights into the biological basis of Alzheimer disease (AD) to enable timely and accurate diagnosis, estimate future burden, and support therapeutic trials. Current cerebrospinal fluid and molecular neuroimaging biomarkers fulfill these criteria but lack the scalability and simplicity necessary or widespread application. Blood biomarkers of adequate effectiveness have the potential to act as first-line diagnostic and prognostic tools, and offer the possibility of extensive population screening and use that is not limited to specialized centres Accelerated progress in our understanding of the biochemistry of brain-derived tau protein and advances in ultrasensitive technologies have allowed for the development of AD-specific phosphorylated tau (p-tau) biomarkers in blood. In this Review we discuss how new information on the molecular processing of brain p-tau and secretion of specific fragments into biofluids is informing blood biomarker development, enabling the evaluation of preanalytical factors that affect quantification, and informing harmonized protocols for blood handling. We also review the performance of blood p-tau biomarkers in the context of AD and discuss their potential contexts of use for clinical and research purposes. Finally, we highlight outstanding ethical, clinical and

The Asparaginyl Endopeptidase Legumain: An Emerging Therapeutic Target and Potential Biomarker for Alzheimer’s Disease

“…Nevertheless, challenges remain in the definition of preclinical AD and standardization of biomarkers that can identify preclinical stage. Concentration of amyloid-β 42 (Aβ 42 ) in CSF, phosphorylated tau (P-tau) in CSF, P-tau181 and P-tau231 in the plasma and Aβ positron-emission tomography (PET) imaging are helpful pathophysiological markers for detecting preclinical phase of the disease, but not yet recognized as specific biomarkers to confirm early diagnosis [ 73 , 74 , 75 ]. Other early signs of AD and dementia, such as sleep disorders, apathy, retinal amyloid imaging, and CSF tau368 and plasma P-tau217 levels are still being investigated [ 76 , 77 , 78 , 79 ].…”

Long-Term Depression-Inducing Low Frequency Stimulation Enhances p-Tau181 and p-Tau217 in an Age-Dependent Manner in Live Rats

“…P-Tau in the brain and its subsequent release into CSF and blood is a dynamic process that changes during disease evolution [5,12]. Although reports from various memory clinics indicate that p-Tau181, p-Tau217, and p-Tau231 distinguish AD from controls with high accuracy for very early AD diagnosis [13,14], the generation of these p-Tau species in patients' brains, in particular learning and memory processes, is still unclear. Also, the phosphorylation patterns of physiological and pathological tau are surprisingly similar and heterogenous, making it difficult to identify specific modifications as therapeutic targets [3,[15][16][17].…”

The Feasibility of Early Alzheimer’s Disease Diagnosis Using a Neural Network Hybrid Platform

“…CSF provides a means to assess neurodegenerative processes in the brain through the identification of disease-associated molecules. These molecules most often are proteins or protein fragments, including the amyloid β-protein (Aβ) and tau [ 20 , 22 , 23 , 24 , 25 , 26 , 27 ], which are amenable to analysis using a variety of techniques, including surface-enhanced Raman spectroscopy (SERS) [ 28 , 29 ]. The raw spectral information collected from CSF covers a huge multi-dimensional dataset.…”