Dataset Information

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

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.

SUBMITTER: Zhang N

PROVIDER: S-EPMC7287025 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Zhang Nan N Gu Dongmei D Meng Meng M Gordon Marc L ML

Frontiers in aging neuroscience 20200604

<h4>Background</h4>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 <i>in vivo</i>.<h4>Methods</h4>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 ...[more]

PMID: 32581773

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Project description:The co-existence of multiple pathologies and proteins is a common feature in the brains of cognitively impaired elderly individuals. Transactive response DNA-binding protein (TDP-43) has been discovered to accumulate in limbic brain regions of a portion of late-onset Alzheimer's disease (AD) patients, in addition to amyloid-? and ? protein. However, it is not yet known whether the TDP-43 species in the AD brain differ in their composition, when compared among different AD cases and to frontotemporal lobar degeneration cases with TDP-43 inclusions (FTLD-TDP). Furthermore, it is not known whether TDP-43 pathology in AD is related to symptoms of the frontotemporal dementia (FTD) spectrum. In this study, we investigated the molecular pattern of TDP-43 lesions with five different antibodies against different phosphorylated (pTDP-43) and non-phosphorylated TDP-43 epitopes. We analyzed a cohort of 97 autopsy cases, including brains from 20 non-demented individuals, 16 cognitively normal pathologically-defined preclinical AD (p-preAD), 51 neuropathologically-confirmed AD cases and 10 FTLD-TDP cases as positive controls. We observed distinct neuropathological patterns of TDP-43 among AD cases. In 11 neuropathologically-confirmed AD cases we found dystrophic neurites (DNs), neuronal cytoplasmic inclusions (NCIs) and/or neurofibrillary tangle (NFT)-like lesions not only positive for pTDP-43409/410, but also for pTDP-43 phosphorylated at serines 403/404 (pTDP-43403/404) and non-phosphorylated, full-length TDP-43, as seen with antibodies against C-terminal TDP-43 and N-terminal TDP-43. These cases were referred to as ADTDP?+?FL because full-length TDP-43 was presumably present in the aggregates. FTLD-TDP cases showed a similar molecular TDP-43 pattern. A second pattern, which was not seen in FTLD-TDP, was observed in most of p-preAD, as well as 30 neuropathologically-confirmed AD cases, which mainly exhibited NFTs and NCIs stained with antibodies against TDP-43 phosphorylated at serines 409/410 (pTDP-43409, pTDP-43409/410). Because only phosphorylated C-terminal species of TDP-43 could be detected in the lesions we designated these AD cases as ADTDP?+?CTF. Ten AD cases did not contain any TDP-43 pathology and were referred to as ADTDP-. The different TDP-43 patterns were associated with clinically typical AD symptoms in 80% of ADTDP?+?CTF cases, 63,6% of ADTDP?+?FL and 100% of the ADTDP- cases. On the other hand, clinical symptoms characteristic for FTD were observed in 36,4% of ADTDP?+?FL, in 16,6% of the ADTDP?+?CTF, and in none of the ADTDP- cases. Our findings provide evidence that TDP-43 aggregates occurring in AD cases vary in their composition, suggesting the distinction of different molecular patterns of TDP-43 pathology ranging from ADTDP- to ADTDP?+?CTF and ADTDP?+?FL with possible impact on their clinical picture, i.e. a higher chance for FTD-like symptoms in ADTDP?+?FL cases.

Dataset Information

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

Publications

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

Similar Datasets

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