Associations of Blood and Cerebrospinal Fluid Aβ and tau Levels with Renal Function

Amyloid beta (A beta) and tau play pivotal roles in the pathogenesis of Alzheimer's disease (AD). Previous studies have shown that brain-derived A beta and tau can be cleared through transport into the periphery, and the kidneys may be vital organs involved in the clearance of A beta and tau. However, the effects of deficiency in the clearance of A beta and tau by the kidneys on brain AD-type pathologies in humans remain largely unknown. In this study, we first recruited 41 patients with chronic kidney disease (CKD) and 40 age- and sex-matched controls with normal renal function to analyze the associations of the estimated glomerular filtration rate (eGFR) with plasma A beta and tau levels. To analyze the associations of eGFR with cerebrospinal fluid (CSF) AD biomarkers, we recruited 42 cognitively normal CKD patients and 150 cognitively normal controls with CSF samples. Compared with controls with normal renal function, CKD patients had higher plasma levels of A beta 40, A beta 42 and total tau (T-tau), lower CSF levels of A beta 40 and A beta 42 and higher levels of CSF T-tau/A beta 42 and phosphorylated tau (P-tau)/A beta 42. Plasma A beta 40, A beta 42, and T-tau levels were negatively correlated with eGFR. In addition, eGFR was negatively correlated with CSF levels of T-tau, T-tau/A beta 42, and P-tau/A beta 42 but positively correlated with Mini-Mental State Examination (MMSE) scores. Thus, this study showed that the decline in renal function was correlated with abnormal AD biomarkers and cognitive decline, which provides human evidence that renal function may be involved in the pathogenesis of AD.