TDP-43 Is Elevated in Plasma Neuronal-Derived Exosomes of Patients With Alzheimer's Disease

Background: Recently, TDP-43 has been recognized as a common proteinopathy in the oldest old and a neuropathological comorbidity in patients with Alzheimer's disease (AD). However, since it has a low concentration in cerebrospinal fluid, the presence of TDP-43 in AD is rarely investigatedin vivo. Methods: Twenty-four patients with amyloid PET confirmed AD and 15 healthy controls (HCs) were included in this study. TDP-43 level in plasma neuronal-derived exosomes (NDEs) was measured by enzyme-linked immunosorbent assay. Results: TDP-43 level was elevated in patients with AD compared with HCs (median 1.08 ng/ml, IQR 0.72-1.37 ng/ml vs. median 0.66 ng/ml, IQR 0.48-0.76 ng/ml,P= 0.002). There was no correlation between TDP-43 level and cognitive function, neuropsychiatric symptoms or APOE genotype in patients with AD. Conclusion: This study demonstrated increased TDP-43 accumulation in AD patients by examining plasma NDEs, which may provide a window into the effects of TDP-43 on AD progression.