Plasma phosphorylated-TDP-43 protein levels correlate with brain pathology in frontotemporal lobar degeneration

Foulds, Penelope; Davidson, Yvonne; Mishra, Manjari; Hobson, David J.; Humphreys, Kirsty M.; Taylor, Mark; Johnson, Nancy; Weıntraub, Sandra; Akiyama, Haruhiko; Arai, Tetsuaki; Hasegawa, Masato; Bigio, Eileen H.; Benson, Fiona E.; Allsop, David; Mann, David

doi:10.1007/s00401-009-0594-0

Cited by 88 publications

(66 citation statements)

References 33 publications

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“…When detected with phospho-independent antibody, plasma TDP-43 level is not significantly different between FTLD and AD, with or without TDP-43 pathology; when detected with phospho-dependent antibody, plasma TDP-43 level is higher in patients with TDP-43 pathology than in those without TDP-43 pathology in FTLD, but this phenomenon is not found in AD patients [44]. Recent study finds that the concentration ratio of TDP-43 CSF to blood is about 1:200, suggesting that CSF TDP-43 may originate from blood [45].…”

Section: Plasma and Csf Levels Of Tdp-43 In Admentioning

confidence: 52%

“…Plasma TDP-43 in AD Elevated plasma TDP-43 level is shown in 46 % of FTLD and 22 % of AD cases, compared to 8 % of control subjects, which closely corresponds to the autopsy-confirmed proportion of TDP-43 pathology in their brain [43,44]. When detected with phospho-independent antibody, plasma TDP-43 level is not significantly different between FTLD and AD, with or without TDP-43 pathology; when detected with phospho-dependent antibody, plasma TDP-43 level is higher in patients with TDP-43 pathology than in those without TDP-43 pathology in FTLD, but this phenomenon is not found in AD patients [44].…”

Section: Plasma and Csf Levels Of Tdp-43 In Admentioning

confidence: 76%

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The Role of TDP-43 in Alzheimer’s Disease

Chang

Tan

et al. 2015

Mol Neurobiol

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The transactive response DNA binding protein (TDP-43) has long been characterized as a main hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U, also known as FTLD-TDP). Several studies have indicated TDP-43 deposits in Alzheimer's disease (AD) brains and have robust connection with AD clinical phenotype. FTLD-U, which was symptomatically connected with AD, may be predictable for the comprehension of the role TDP-43 in AD. TDP-43 may contribute to AD through both β-amyloid (Aβ)-dependent and Aβ-independent pathways. In this article, we summarize the latest studies concerning the role of TDP-43 in AD and explore TDP-43 modulation as a potential therapeutic strategy for AD. However, to date, little of pieces of the research on TDP-43 have been performed to investigate the role in AD; more investigations need to be confirmed in the future.

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Section: Plasma and Csf Levels Of Tdp-43 In Admentioning

confidence: 52%

Section: Plasma and Csf Levels Of Tdp-43 In Admentioning

confidence: 76%

The Role of TDP-43 in Alzheimer’s Disease

Chang

Tan

et al. 2015

Mol Neurobiol

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“…In patients with GRN mutations, plasma progranulin level can predict the presence of a mutation and may be an easier and more costeffective screening method (Coppola et al 2008;Ghidoni et al 2008;Finch et al 2009). Preliminary studies looking at plasma TDP-43 levels have unfortunately not shown that they are able to differentiate between different subgroups (Foulds et al 2008;Foulds et al 2009), but further work continues in this area.…”

Section: Bloodmentioning

confidence: 95%

Behavioural Variant Frontotemporal Dementia—Defining Genetic and Pathological Subtypes

Rohrer

2011

J Mol Neurosci

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Behavioural variant frontotemporal dementia (bvFTD) is a clinically, genetically and pathologically heterogeneous neurodegenerative disorder caused by FTLD-tau, FTLD-TDP and FTLD-FUS pathologies. Clinically, patients present with behavioural symptoms that may include one or more of disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative, stereotyped and compulsive/ritualistic behaviour or hyperorality/dietary changes. Cognitive deficits, particularly executive dysfunction, are also seen. Neuroanatomically, patients have frontal and/or temporal lobe atrophy on neuroimaging. However, there is currently no clear correlation between the clinical and neuroanatomical phenotype in life and the underlying pathogenetics. With the advent of clinical trials in bvFTD, establishing the underlying pathology accurately during life will become increasingly important. This review therefore investigates current and future biomarkers that may help make a pathological diagnosis in life, i.e. bvFTD-tau, bvFTD-TDP and bvFTD-FUS, including clinical and neuropsychological data, neuroimaging, blood and CSF markers.

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“…[29][30][31][32] However, the interpretation of those results warrants caution, because we found that general organs exhibited TDP-43 accumulation even in individuals without ALS. Copyright of Neuropathology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission.…”

mentioning

confidence: 65%

Cytoplasmic TDP‐43 accumulation in cells of the adrenal medulla in individuals with or without amyotrophic lateral sclerosis

Okamoto¹,

Amari²,

Fujita

et al. 2014

Neuropathology

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The transactive response DNA-binding protein of 43 kDa (TDP-43) is normally located predominantly in the nucleus, whereas pathological TDP-43 is mostly found in the cytoplasm. Cytoplasmic TDP-43 accumulation has not yet been reported in normal general organs. In our preliminary study, paraffin sections of the general organs of individuals with or without amyotrophic lateral sclerosis (ALS) were immunostained with antibodies against TDP-43 and phosphorylated TDP-43 (pTDP-43). Diffuse and granular immunostaining pattern of TDP-43 and pTDP-43 were observed frequently in the cytoplasm of renal tubular cells, and less frequently in the cells of several organs; however, the majority of these immunoreactivities were nonspecific biotin reactions. Conversely, many TDP-43-positive and pTDP-43-negative cytoplasmic accumulations were observed in the adrenal medulla in every individual (with or without ALS). Skein-like or round inclusions were not observed. The cells in the adrenal medulla were well preserved, and the cytoplasmic TDP-43 accumulations were frequent in the cells of all routine autopsy cases without loss of nuclear TDP-43 immunostaining; therefore, we considered that this was a physiological phenomenon. This is the first study that demonstrated the cytoplasmic accumulation of TDP-43 in routinely autopsied cases.

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Plasma phosphorylated-TDP-43 protein levels correlate with brain pathology in frontotemporal lobar degeneration

Cited by 88 publications

References 33 publications

The Role of TDP-43 in Alzheimer’s Disease

The Role of TDP-43 in Alzheimer’s Disease

Behavioural Variant Frontotemporal Dementia—Defining Genetic and Pathological Subtypes

Cytoplasmic TDP‐43 accumulation in cells of the adrenal medulla in individuals with or without amyotrophic lateral sclerosis

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