JASN Correspondence Questions Interpretation of Alzheimer’s CSF Biomarkers in CKD

Correspondence in the Journal of the American Society of Nephrology questions a systematic review and meta-analysis concluding that associations between kidney function and Alzheimer’s disease cerebrospinal fluid (CSF) biomarkers were heterogeneous and generally null. The authors highlight an omitted observational study by Hajjar and colleagues involving 973 participants from the Goizueta Alzheimer’s Disease Research Center; the meta-analysis included 10 studies reporting CSF biomarkers.

In the omitted study, lower eGFR was associated with lower CSF Aβ42 (P=0.002), higher tau (P<0.0001), higher phosphorylated tau (P=0.0002), and a lower Aβ42/tau ratio (P<0.0001). Associations were more pronounced among cognitively impaired participants. The correspondence also cites a study by Dittrich and colleagues in which lower eGFR correlated with lower CSF Aβ42 and higher total tau among amyloid-positive participants, but not amyloid-negative participants.

The authors argue that these findings warrant caution when considering CSF testing as an alternative to blood-based Alzheimer’s biomarkers in CKD. However, the correspondence presents no updated pooled analysis or effect-size estimates, so the impact of including the omitted study remains uncertain. The reported associations do not establish causality or quantify diagnostic accuracy in CKD; the authors propose that kidney function may affect CSF biomarkers less than plasma biomarkers.