BACKGROUND: Despite the close association of Alzheimer's disease (AD) with muscle decline, the biomarkers of age-related muscle loss, termed sarcopenia, in AD remain elusive. OBJECTIVES: We investigated the plasma neurofilament light (NfL) chain levels as potential biomarkers of sarcopenia in AD patients. DESIGN SETTING, PARTICIPANTS, MEASUREMENTS: We conducted a cross-sectional, observational study on older adults, including controls and patients with AD (n = 38-44/group). We measured the frequency of sarcopenia, body composition, handgrip strength (HGS), gait speed, and short physical performance battery (SPPB) in the study participants. We also measured the plasma NfL levels as marker of neurodegeneration. RESULTS: AD was associated with a higher frequency of sarcopenia and reduced HGS, gait speed, and SPPB scores (all p <
0.05). The higher plasma NfL levels in AD patients were correlated with lower HGS, gait speed, and SPPB scores (all p <
0.05). Plasma NfL exhibited moderate accuracy in diagnosing sarcopenia (area under the curve
AUC = 0.701, p <
0.001) and functional dependency (AUC = 0.772, p <
0.001). Among different subgroups of AD, moderate AD was associated with more advanced sarcopenia and functional dependency than early and mild AD. Patients with AD also exhibited heightened inflammation and oxidative stress. CONCLUSION: Altogether, plasma NfL may be a preliminary tool in diagnosing advanced sarcopenia and functional dependency in AD. The study is relevant to non-ambulant and/or comatose AD patients with sarcopenia.