Biomarkers

Depression is an established risk factor for neurodegenerative diseases, including Alzheimer's disease (AD). While blood-based biomarkers (BBMs) have been promising for early detection of neurodegeneration, their relationship with depressive symptoms remains controversial. We explored the cross-sectional relationship between depression and BBMs of neurodegeneration and AD pathology (t-tau, NfL, GFAP, and p-tau181) using ultrasensitive immunoassay.

The current study comprises the Offspring (exam 9) and Omni 1 (exam 4) cohorts of the Framingham Heart study (FHS) who completed their visits between 2011 and 2014. Depression was considered a binary variable (yes/no) and defined as having a score ≥16 on the Center for Epidemiologic Studies Depression Scale or reporting antidepressant use. Single Molecule Array (SIMOA) assays were used to assess plasma levels of t-tau, NfL, GFAP, and p-tau181. All BBM values were log-transformed and standardized. Multivariable regression models were adjusted for (1) sex, age, cohort, and additionally (2) education, APOE4 status, FHS cardiovascular risk score, estimated glomerular filtration rate, and C-reactive protein.

Among 2,466 participants (mean age 69.8 years, 44.9 % male), 19.8% met criteria for depression (see Table 1 for clinical characteristics). Depression was significantly associated with higher t-tau levels in both model 1 (β±SE =0.24±0.05, p <0.001) and model 2 (0.21±0.05, p <0.001). No associations were found between depression and p-tau 181, NfL, or GFAP, as shown in Table 2.

Depression was associated with higher t-tau levels in these cohorts. While current findings corroborate previous studies showing that depressive symptoms were not associated with plasma biomarkers of AD pathology, the positive association with t-tau level suggests the involvement of neuronal injury.