AD Biomarkers in Chronic Kidney Disease and Kidney Transplant
Aditi Gupta, Jill K Morris, Paul J. Kueck, Anneka Blankenship, Jonathan D Mahnken, Kate Young- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Blood biomarkers of Alzheimer’s disease (AD) are elevated in chronic kidney disease (CKD). Whether this is due to deceased kidney clearance or increased production, and how they change with kidney transplant (KT), is unclear.
Method
We examined serum AD biomarkers from CKD patients pre‐ to post‐KT and compared findings with controls without CKD or AD. Analyses were performed on a Simoa HD‐X, using pTau181 and Neuro 4 Plex E assays.
Age was used for covariate adjustment in linear mixed models (LMM) analyzing phosphorylated tau 181 (ptau181), neurofilament light (NfL), amyloid beta (AB42, AB40, 42/40), and glial fibrillary acidic protein (GFAP). Change in p‐tau181 was our primary outcome. LMM included age and levels for control, pre‐KT, or 12‐weeks or 1‐year post‐KT. Based on residual patterns, the natural log (In) of each measure was used for final analyses. Linear contrasts were used to generate estimated differences between group/time points from age‐adjusted models. These included averaged pre‐KT, post‐KT, and control comparisons. Two degree‐of‐freedom tests compared the post‐KT measures to pre‐KT and controls.
Result
The 59 CKD patients were 52±12 years old and 13 controls were 51±8 years old. Pre‐KT, ln(p‐tau181) was higher than controls (p<0.0001) and post‐KT (p<0.0001) (Figure). Post‐KT p‐tau181 greatly decreased but remained higher than controls (p = 0.0004). There was no difference between 12 weeks and 1 year post‐KT levels (p = 0.70). ln(pTau) increased with age (p = 0.06). ln(NfL) followed a similar pattern; pre‐KT levels were higher than controls (p<0.0001) and post‐KT (p<0.0001). Post‐KT levels decreased but remained higher than controls (p<0.0001). 12‐week and 1‐year post‐KT levels did not differ (p = 0.57). Levels increased with age (p<0.0001). Pre‐KT AB42 was higher than controls (p<0.0001) and post‐KT (p<0.0001). Post‐KT, levels decreased but remained higher than controls (p = 0.005) and continued declining 1‐year post‐transplant (p = 0.01). In(AB40) and In(GFAP) showed the same pattern. The AB42/AB40 was not different pre‐KT vs controls (p = 0.58) and did not change following KT. Cognitive function improved post‐KT. Patients with residual kidney function had lower baseline levels of AD blood biomarkers.
Conclusion
In severe CKD, blood biomarkers of AD are dependent on kidney function and caution should be used in interpreting them.