Glymphatic Efficiency Is a Critical Factor for Using Abnormal Tau in Peripheral Tissues as Biomarker for Alzheimer's Disease.

Alzheimer's Disease or other dementias are characterized by the accumulation of abnormal tau and amyloid β peptides in brains. Therefore, abnormal tau and amyloid peptides in peripheral tissues or blood have been explored as diagnostic biomarkers. On the other hand, recent studies have revealed glymphatics a special drainage system for brain's wastes. We aimed to investigate whether effectiveness of glymphatic system affects the quantity of abnormal tau in the peripheral tissues. We have previously shown that aged IL33 KO (Il33 ^-/-) mice develop Alzheimer's like disease. Despite a large quantity of abnormal tau in brains, Il33 ^-/- mice showed a much lower amount of abnormal tau drained to the peripheral tissues kidneys than in wild type mice. Our further study showed that it was caused by defective glymphatic drainage since Il33 KO impaired glymphatics. Thus, it is necessary to identify biomarkers, which can evaluate efficiency of glymphatic drainage. Simultaneous measurement of these biomarkers and abnormal tau in peripheral tissues or blood may be critical for accurate diagnosis of Alzheimer's disease.