INTRODUCTION: Alzheimer's disease (AD) blood biomarkers hold clinical potential but their concentration may vary with somatic conditions.

METHODS: We investigated the concentration of six AD blood biomarkers in relation to multimorbidity as disease count and four multimorbidity patterns in 2290 cognitively unimpaired older adults.

RESULTS: Levels of phosphorylated tau (p‐tau)181, p‐tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) increased with increasing number of diseases. In multi‐adjusted regressions, compared to individuals without multimorbidity, the anemia/sensory impairment pattern was associated with altered levels of all biomarkers except amyloid beta (Aβ)42/40, GFAP, and total tau (p‐tau181: β = 0.18, 95% confidence interval [CI]: 0.08, 0.28; p‐tau217: β = 0.11, 95% CI: 0.03, 0.18; NfL: β = 0.14, 95% CI: 0.06, 0.21) and the cardiometabolic/inflammatory pattern was associated with altered levels of all biomarkers except Aβ42/40 and GFAP (p‐tau181: β = 0.24, 95% CI: 0.12, 0.36; p‐tau217: β = 0.23, 95% CI: 0.14, 0.32; NfL: β = 0.32, 95% CI: 0.23, 0.40; total tau: β = 0.23, 95% CI: 0.07, 0.39). Results remained unchanged after excluding those who developed dementia in 15 years.

DISCUSSION: More diseases and specific multimorbidity patterns altered the levels of several AD blood biomarkers, highlighting caution when using them in adults with complex health profiles.

Highlights: In cognitively unimpaired older adults blood biomarkers of Alzheimer's disease varied depending on the number of chronic diseases and specific patterns of multimorbidity. Phosphorylated tau (p‐tau)181, p‐tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein levels increased along with increasing numbers of chronic diseases. P‐tau181, p‐tau217, and NfL levels were significantly higher in individuals in the anemia/sensory impairment and cardiometabolic/inflammatory multimorbidity patterns compared to those without multimorbidity. Results remained unchanged after excluding participants who developed dementia during 15‐year follow‐up. In cognitively unimpaired older adults blood biomarkers of Alzheimer's disease varied depending on the number of chronic diseases and specific patterns of multimorbidity.Phosphorylated tau (p‐tau)181, p‐tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein levels increased along with increasing numbers of chronic diseases.P‐tau181, p‐tau217, and NfL levels were significantly higher in individuals in the anemia/sensory impairment and cardiometabolic/inflammatory multimorbidity patterns compared to those without multimorbidity.Results remained unchanged after excluding participants who developed dementia during 15‐year follow‐up.