Detection of Alzheimer's Disease Neuropathology in Chronic Kidney Disease: Current State and Future Directions

The prevalence of both chronic kidney disease (CKD) and Alzheimer's disease (AD) increases with age. With the rise in average life expectancy, clinicians will be more likely to encounter patients with both CKD and cognitive concerns, including some with AD neuropathology. The prevalence of AD neuropathology and the nature of the interaction between AD neuropathology and vascular brain alterations in individuals with CKD are unclear. AD blood-based biomarkers (BBM) are promising tools for detecting AD neuropathology and are being reviewed by the FDA for clinical use. However, AD BBMs do not perform reliably in CKD and can be elevated even in the absence of AD neuropathology (false positive). AD cerebrospinal fluid (CSF) biomarkers are also altered in CKD, further complicating the detection of AD neuropathology in this population. It is important for clinicians to understand the limitations of AD BBMs and perhaps CSF biomarkers in the real world, where there is a higher prevalence of CKD and other comorbidities compared to the population samples in which they have been studied. Even if the prevalence of AD neuropathology in CKD is not higher than that in the general population, it is important to accurately detect AD neuropathology among individuals with CKD, so that the new anti-amyloid monoclonal antibodies can be used appropriately. This special article addresses the concerns with the use of AD BBM in the detection of AD neuropathology and the caution needed while using AD BBMs in clinical care.