Chronic Kidney Disease May Limit Accuracy of Alzheimer Blood Biomarkers

Reduced kidney function may undermine the accuracy of blood-based biomarkers used to predict Alzheimer disease (AD) outcomes, according to findings published in Alzheimer’s & Dementia.

Blood biomarkers have emerged as promising tools for detecting AD pathology, but their interpretation can be confounded by comorbid health conditions. Researchers examined whether reduced kidney function affected the predictive accuracy of plasma biomarkers for cognitive decline and neuroimaging outcomes.

The study included 333 older adults without dementia, of whom the mean (SD) age was 73 (7.3) years, 59% were men, and 35% were APOE ε4 carriers. At baseline, 17% had no chronic kidney disease (CKD) or stage 1 CKD, 65% had stage 2 CKD, and 18% had stage 3 CKD. No participants had advanced CKD (stages 4 to 5). Over a mean follow-up of 6.4 years, participants underwent serial cognitive testing and neuroimaging.

In sum, this study shows that kidney function, as estimated by eGFR levels, affects the levels of circulating blood proteins used as biomarkers for AD and concomitant pathologies…

Baseline comparisons showed that participants with stage 3 CKD were older (mean [SD] age, 77 [7.8] years) and more likely to have lower Montreal Cognitive Assessment scores than those without CKD (24.2 vs 26.2; P =.01). Plasma biomarker concentrations, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), amyloid beta 42, and phosphorylated tau₂₃₁, were significantly elevated in participants with stage 3 CKD. For example, mean NfL levels were 46 pg/mL in stage 3 CKD, compared with 25 pg/mL in no CKD/stage 1 CKD and 27 pg/mL in stage 2 CKD (P < .001).

Across the cohort, higher plasma NfL and GFAP were associated with poorer performance on tests of executive function and memory, as well as greater cortical thinning on MRI. However, the predictive strength of NfL and other biomarkers varied by kidney function.

In longitudinal analyses, plasma NfL strongly predicted decline in language, executive function, and visuospatial outcomes among those without CKD or with stage 2 CKD. For example, on the Boston Naming Test, those without CKD or with stage 1 CKD showed a significant decline (β = –0.05; P < .0001), while the association was minimal and nonsignificant in those with stage 3 CKD (β = 0.002; P = .57). Similar patterns were observed for neuroimaging outcomes, with weaker associations in participants with reduced kidney function.

The study is limited by the absence of participants with severe CKD, restricting generalizability to later disease stages.

“In sum, this study shows that kidney function, as estimated by eGFR [estimated glomerular filtration rate] levels, affects the levels of circulating blood proteins used as biomarkers for AD and concomitant pathologies and moderates the association between some of these blood-based biomarkers and key clinical outcomes,” the study authors concluded.

Disclosures: This research was supported by the National Institutes of Health, the Alzheimer’s Association, the Vanderbilt Alzheimer’s Disease Research Center, the Swedish Research Council, the Swedish Alzheimer Foundation, Hjärnfonden Sweden, Fondation Recherche Alzheimer, Familjen Rönströms Stiftelse, Swedish State Support for Clinical Research, the Alzheimer Drug Discovery Foundation, the European Union’s Horizon Europe Research and Innovation Programme, the National Institute for Health and Care Research, the US Department of Veterans Affairs, and the National Institute on Aging. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.