Impaired Kidney Function Linked to Alzheimer’s Biomarkers But Not Dementia

New research highlights an association between impaired kidney function and increased levels of Alzheimer's disease (AD) biomarkers, particularly neurofilament light chain, but does not indicate an increased risk of dementia.1

“Our study found that when the kidneys are not functioning properly, there may be higher levels of Alzheimer’s biomarkers in the blood,” said study investigator Francesca Gasparini, MD, research assistant at the Karolinska Institute, in a press release. “While we did not find that having reduced kidney function increased the risk of developing dementia, we did find that impaired kidney function may accelerate the onset of dementia in people who have higher levels of biomarkers. This highlights the need for doctors to consider kidney function when interpreting results of Alzheimer’s biomarkers in the blood.”2

Investigators conducted a longitudinal population-based cohort study in older adults, incorporating cross-sectional biomarker analyses and prospective dementia follow-up, to evaluate the associations between estimated glomerular filtration rate (eGFR), blood-based biomarkers of Alzheimer's disease, and dementia development.1

Gasparini and colleagues extracted data from an ongoing longitudinal population-based study, the Swedish National Study on Aging in Kungsholmen. They assessed kidney function using serum creatinine-based eGFR, and used peripheral blood samples with the Simoa platform to measure AD biomarkers, including amyloid beta (Aβ42/40), phosphorylated tau (p-tau181) and (p-tau217), and total tau (t-tau) proteins, neurofilament light chain, and glial fibrillary acidic protein (GFAP). DSM-IV criteria were used to diagnose dementia.1

The study included 2279 participants ≥ 60 years of age without dementia and with available blood samples of AD biomarkers and serum creatinine at baseline. The average age was 72 years. Investigators categorized participants into a reference group of preserved kidney function (n = 1722) and a comparison group, those with impaired kidney function, defined as eGFR < 60 mL/min/1.73 m2 (n =557).1

Among the 24% of participants with impaired kidney function, individuals were older, more often female, and had an increased comorbidity burden compared with those with preserved kidney function. At baseline, they also had higher concentrations of tau proteins, neurofilament light chain, and GFAP and lower levels of Aβ42/40 (P < .001).1 

Across the patient population, investigators identified 362 dementia cases, 221 in the preserved kidney function group and 141 in the impaired kidney function group. Unadjusted incidence rates of dementia per 100 person-years were 1.46 (95% Confidence Interval [CI], 1.28–1.67) and 3.72 (95% CI, 3.16–4.39), respectively.1

Investigators employed quantile regression models to assess the cross-sectional associations between eGFR and AD biomarkers. Upon analysis, they found an association between decreased eGFR and increased median levels of t-tau, p-tau181 and p-tau217, neurofilament light chain, and GFAP, following a nonlinear relationship (P for nonlinearity ≤.001 for all). Neurofilament light chain exhibited the strongest association with reduced kidney function, with an increased concentration of approximately 1 standard deviation at 30 mL/min/1.73 m2 of eGFR (β, 0.88; 95% CI, 0.80–0.95).1 

Cox regression models examined the association of kidney function and biomarkers with incident dementia. Those with impaired kidney function did not show an increased risk of dementia (Hazard Ratio [HR], 0.93 [95% CI 0.72–1.21]) when compared with preserved kidney function independently from confounders. No increased risk of dementia was observed with increased severe kidney impairment, including patients with eGFR of 45 mL/min/1.73 m2 (HR, 1.00; 95% CI, 0.85–1.18) and 30 mL/min/1.73 m2 (HR, 0.98; 95% CI, 0.65–1.48) compared with the reference group.1

Upon stratified analyses, investigators observed a stronger association between increased levels of neurofilament light chain and dementia among individuals with impaired kidney function (HR, 3.85; 95% CI, 1.87–7.95) compared with those with preserved kidney function (HR, 1.84; 85% CI, 1.34–2.53). Among individuals with impaired kidney function, there was a significant association between increased levels of t-tau and dementia (HR, 1.72; 95% CI, 1.17–2.53). Between those with impaired and preserved kidney function, Aβ42/40 was not significantly associated with an increased dementia risk.1

Sensitivity analyses supported a correlation between increased neurofilament light chain and impaired kidney function (HR, 1.47; 95% CI, 1.26 - 1.70) compared to preserved kidney function (HR, 1.14; 95% CI, 1.03-1.26; P = .005). There were no significant associations for t-tau and GFAP.1

“When looking at these biomarkers in older adults, keeping an eye on kidney health may be more important than one might think,” concluded investigators. “Monitoring kidney health may help clinicians better interpret these biomarkers and identify who might be at risk for faster disease progression.2

References

1. Gasparini F, Valletta M, Vetrano DL, et al. Kidney Function, Alzheimer Disease Blood Biomarkers, and Dementia Risk in Community-Dwelling Older Adults. Neurology. 2026;106(1). doi:https://doi.org/10.1212/wnl.0000000000214446

2. Poor kidney health linked to higher levels of Alzheimer’s biomarkers in blood. EurekAlert! Published December 3, 2025. Accessed December 4, 2025. https://www.eurekalert.org/news-releases/1107995