Abstract
BACKGROUND: 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. METHOD: 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. RESULT: 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. CONCLUSION: 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.