The following is a summary of “Explaining the Variability of Alzheimer Disease Fluid Biomarker Concentrations in Memory Clinic Patients Without Dementia,” published in the March 2024 issue of Neurology by Bouteloup et al.

Researchers conducted a retrospective study to identify how much clinical features of Alzheimer’s disease (AD) and other unrelated factors contribute to variations in fluid biomarker levels.

They involved 2,323 individuals experiencing cognitive complaints or mild cognitive impairment with 26 French memory clinics under the MEMENTO study. Initial assessments included clinical and neuropsychological evaluations, brain MRI, amyloid-PET, optional CSF analysis, and blood sampling, with biomarker levels analyzed using the Simoa-HDX analyzer. Linear regression analysis was employed to model biomarker concentrations based on clinical features of AD (cognition, AD genetic risk score, and brain atrophy). Various covariates were included in the final models using stepwise selection and least absolute shrinkage and selection operator (LASSO), encompassing routine tests, inflammation markers, demographics, treatments, comorbidities, and sample handling.

The results showed  2,257 participants, with a median age of 71.7, 61.8% women, and 55.2% with high educational levels, were included in the analysis. For blood biomarkers, the proportions of variance explained by clinical features of AD were 13.7% for neurofilaments (NfL), 11.4% for p181-tau, 3.0% for Aβ-42/40, and 1.4% for total-tau. In final models accounting for non-AD-related factors, age, routine biological tests, inflammatory markers, and preanalytical sample handling mainly explained the variance. In CSF, clinical features of AD explained 24.8% for NfL, 22.3% for Aβ-42/40, 19.8% for total-tau, and 17.2% for p181-tau. In contrast to blood biomarkers, cognition explained the most significant proportion of variance after adjusting for covariates. The top LASSO covariates explained most variance, and blood biomarkers’ predictive accuracy for A+ and T+ status held steady post-adjustment.

Investigators concluded that age primarily explained blood biomarker variations in AD, with lesser influence from cognition, brain shrinkage, and genetics, unlike CSF measures.

Source: neurology.org/doi/10.1212/WNL.0000000000209219