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. 2020 Jun 4:12:166.
doi: 10.3389/fnagi.2020.00166. eCollection 2020.

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

Nan Zhang  1   2 , Dongmei Gu  3 , Meng Meng  2 , Marc L Gordon  4   5
Affiliations

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

Nan Zhang et al. Front Aging Neurosci. .

Abstract

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 investigated in 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.

Keywords: APOE; Alzheimer’s disease; TDP-43; cognitive function; exosome; neuropsychiatric symptoms.

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Figures

FIGURE 1
FIGURE 1
Plasma neuronal-derived exosomes identified with TEM and NTA. (A) A representative image detected with transmission electron microscopy of exosomes extracted from an AD patient. The scale bar equals 100 nm. (B) A representative plot of size/concentration determined with nanoparticle tracking analysis for plasma exosomes derived from an AD patient.
FIGURE 2
FIGURE 2
Protein concentrations of plasma neuronal-derived exosomes detected with ELISA. (A) Median CD81 level was lower in patients with AD compared to HCs. (B) Median normalized TDP-43 concentration was higher in patients with AD compared to HCs. AD, Alzheimer’s disease; HC, healthy control.
FIGURE 3
FIGURE 3
The comparison of TDP-43 concentration between patients with and without specific neuropsychiatric symptom clusters, and APOE ε4 carriers and non-carriers in AD. (A–E) There were no correlations between TDP-43 and psychosis, hyperactivity, affect, apathy/vegetative, and motor disturbance measured with NPI in patients with AD (P > 0.05). (F) The difference in TDP-43 level between APOE ε4 carriers and non-carriers of AD patients was not statistically significant (P > 0.05).
See this image and copyright information in PMC

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