Critical Comparison of Different Biomarkers for Alzheimer's Disease in a Clinical Setting

Background: Biomarkers of neuronal injury and amyloid pathology play a pivotal role in the diagnosis of Alzheimer's disease (AD). The degree of AD biomarker congruence is still unclear in clinical practice. Objective: Diagnosis of AD with regard to the congruence of the clinical diagnosis and different biomarkers. Methods: In this prospective cross-sectional observational study, 54 patients with mild cognitive impairment or dementia due to AD or not due to AD were investigated. Biomarkers of neuronal injury were medial temporal lobe atrophy (MTA) on magnetic resonance imaging (MRI) and tau concentration in the cerebrospinal fluid (CSF). CSF A beta(1-42) and amyloid-targeting positron emission tomography (PET) were considered as biomarkers of amyloid pathology. Results: Forty cases were diagnosed as AD and 14 cases were diagnosed as non-AD based on clinical and routine MRI assessment. AD cases had higher MTA scores, higher levels of CSF tau and lower levels of CSF A beta(1-42), and higher amyloid load on PET compared to the non-AD group. In the AD group, completely consistently pathological biomarkers were found in 32.5%, non-pathological in 5%. In 62.5% the findings were inconsistent. Congruence of biomarkers was 67.5% for neuronal injury and for amyloid dysfunction, respectively. In two patients, clinical diagnosis switched to non-AD due to completely consistent non-pathological biomarker findings. The criteria of the international working group were met in 75.0%. Conclusion: Surprisingly, the number of completely congruent biomarkers was relatively low. Interpretation of AD biomarkers is complicated by multiple biomarker constellations. However, the level of biomarker consistency required to reliably diagnose AD remains uncertain.