Do Amyloid and Tau Ratios Mitigate the Impact of Reduced eGFR on Blood Alzheimer's Biomarkers?

In their recent JASN article, Lin et al.1 provide a timely synthesis demonstrating that lower kidney function is associated with higher concentrations of several blood biomarkers used in Alzheimer's disease and related dementia evaluation. In their adjusted meta-analyses, each 1 ml/min per 1.73 m2 decrement in eGFR corresponded to higher blood neurofilament light, glial fibrillary acidic protein, and Aβ40 concentrations.1 These findings are particularly relevant as blood-based biomarkers move from research settings toward structured clinical adoption. Recent diagnostic and implementation frameworks increasingly treat plasma biomarkers as actionable evidence. The Alzheimer's Association 2024 revised criteria explicitly incorporate plasma biomarkers into Alzheimer's disease diagnosis and staging,2 and a 2025 clinical practice guideline provides performance-based, brand-agnostic recommendations for blood-based biomarker testing within specialized care settings (including Aβ42/Aβ40 and phosphorylated tau analytes).3 As these frameworks begin to shape real-world diagnostic pathways—and potentially downstream access to confirmatory testing—patients with CKD may be more likely to have biomarker values shifted toward “positive” ranges if reduced clearance through the kidneys contributes to higher circulating concentrations. A focused, answerable question using Lin et al.’s existing dataset is whether ratio-based measures prioritized in current guidance appear comparatively robust to kidney dysfunction. Their narrative synthesis suggests that the plasma Aβ42/Aβ40 ratio was often not associated with eGFR, unlike several single-analyte concentrations.1 Could the authors provide pooled effect estimates (or, where pooling is not feasible, standardized summary statistics) specifically for Aβ42/Aβ40 and phosphorylated-to-total tau ratios when available? This would help clarify whether ratios mitigate kidney-related shifts, consistent with prior work showing that tau ratios attenuate associations with kidney dysfunction.4 Such a focused extension would directly support nephrology and dementia clinicians navigating guideline-driven blood testing in populations where CKD is common.