Impaired kidney function influences AD blood biomarkers but not dementia risk

Among individuals without cognitive impairment, those with impaired kidney function exhibit increased levels of Alzheimer’s disease (AD) blood biomarkers, although they do not appear to be at increased risk of dementia compared with those who have preserved kidney function, according to new research.

In a cohort of 2,279 dementia-free participants (median age 72 years, 62 percent female, 29 percent were APOE ε4 allele carriers) from the Swedish National Study on Aging and Care in Kungsholmen, lower eGFR (<60 mL/min/1.73 m²) was associated with higher median concentrations of t-tau, p-tau181, p-tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) (p≤0.001 for all). NfL showed the strongest association with reduced kidney function. [Neurology 2026;doi:10.1212/WNL.0000000000214446]

“For instance, the concentration of NfL increased by approximately 1 standard deviation at 30 mL/min/1.73 m² of eGFR (β, 0.88, 95 percent confidence interval [CI], 0.80–0.95), while the other biomarkers presented smaller increases (t-tau181: β, 0.22, 95 percent CI, 0.09–0.35; t-tau217: β, 0.20, 95 percent CI, 0.10–0.31; t-tau: β, 0.24, 95 percent CI, 0.05–0.42; GFAP: β, 0.10, 95 percent CI, 0.03–0.16),” the authors noted.

These associations were consistent in an analysis excluding the 362 participants who received a diagnosis of dementia over the 16-year follow-up (mean 8.3 years).

Not a risk factor

“However, the presence of impaired kidney function did not independently increase the risk of dementia but rather seemed to accelerate dementia onset among participants with altered levels of biomarkers linked to neurodegeneration,” the authors pointed out.

Compared with eGFR ≥60 mL/min/1.73 m², eGFR <60 mL/min/1.73 m² was not significantly associated with an increased hazard of dementia (hazard ratio [HR], 0.93, 95 percent CI, 0.72–1.21). Similar results were observed when a time-varying approach for eGFR was used (45 vs ≥60 mL/min/1.73 m²: HR, 1.00, 95 percent CI, 0.85–1.18; 30 vs ≥60 mL/min/1.73 m²: HR, 0.98, 95 percent CI, 0.65–1.48).

The association between elevated NfL and dementia risk was more pronounced among participants with impaired kidney function (HR, 3.85, 95 percent CI, 1.87–7.95) than among those with preserved kidney function (HR, 1.84, 95 percent CI, 1.34–2.53). Meanwhile, the association between elevated levels of t-tau and dementia risk was observed only among participants with impaired kidney function (HR, 1.72, 95 percent CI, 1.17–2.53).

The association of p-tau181, p-tau217, and GFAP with dementia did not differ between participants with impaired kidney function and those with preserved kidney function.

Careful interpretation

“When the kidneys are not functioning properly, there may be higher levels of Alzheimer’s biomarkers in the blood,” according to first study author Dr Francesca Gasparini from Karolinska Institutet in Stockholm, Sweden.

The study findings underscore the importance of considering kidney function when interpreting results of AD biomarkers in the blood, Gasparini added.

“When looking at these biomarkers in older adults, keeping an eye on kidney health may be more important than one might think. Monitoring kidney health may help clinicians better interpret these biomarkers and identify who might be at risk for faster disease progression,” she said.

For the study, Gasparini and colleagues measured eGFR based on serum creatinine. They quantified AD biomarkers from peripheral blood samples using the Simoa platform.

Of the participants, 557 (24 percent) had impaired kidney function (eGFR <60 mL/min/1.73 m²). These participants were older, mostly female, and had a higher comorbidity burden compared with those with preserved kidney function.