Temporal Changes in Alzheimer's Disease-Related Biomarkers in the CSF of Cognitively Normal Subjects at Different Ages: The Chongqing Ageing and Dementia Study

Revealing the temporal evolution of cerebrospinal fluid (CSF) biomarkers during aging is critical to understanding disease pathogenesis and developing early diagnoses and interventions for Alzheimer's disease (AD). CSF was obtained from 549 cognitively normal subjects between 18 and 93 years of age. 12 AD-related biomarkers were evaluated, including amyloid beta (A beta 42, A beta 40, A beta 42/A beta 40 ratio), hyperphosphorylated tau (P-tau), neuronal injury/degeneration (T-tau, NFL, NSE, H-FABP, VILIP-1), neuroinflammation biomarkers (YKL-40, TREM2), and alpha-synuclein (alpha-synuclein). Associations between these biomarkers and age as well as apolipoprotein E (APOE) epsilon 4 status were evaluated, and the associations among biomarkers were assessed. CSF A beta 42, P-tau, and T-tau levels exhibited nonlinear associations with age, among which A beta 42 was significantly modulated by APOE epsilon 4 status. Specifically, an accelerated decline in A beta 42 levels occurred at 45.69 years of age in the APOE epsilon 4+ group, which was almost 23 years earlier than that in the APOE epsilon 4- group (68.02 years). The age-related change pattern of CSF P-tau is similar to that of T-tau, with both increasing slightly with age but showing an accelerated change at approximate to 60 years of age in the APOE epsilon 4+ group. All the other biomarkers except for alpha-synuclein were linearly associated with age, and APOE epsilon 4 status had no effect on these associations. Most biomarkers were positively correlated with each other except for A beta 42/A beta 40 ratio. The evolution of AD-related biomarkers in CSF varies throughout the adult lifespan, with the APOE epsilon 4 allele modifying the temporal changes in CSF A beta 42 levels, as well as potentially influencing P-tau and T-tau levels.