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Concentrations of beta-amyloid precursor protein processing products in cerebrospinal fluid of patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration

  • Dementias - Original Article
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Abstract

Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders with heterogeneous clinical presentation but common neuropathological characteristics and pathophysiological substrates, which led to the view of ALS and FTLD representing two manifestations of a clinicopathological spectrum. For both diseases, changes in metabolism of beta-amyloid precursor protein (APP) are reported. In a pilot study, we analyzed cerebrospinal fluid from patients of the ALS-FTLD spectrum for APP processing products. ALS patients show elevated absolute levels of soluble APP and a shift towards the nonamyloidogenic APP processing pathway in contrast to patients with FTLD or ALS + FTLD. Changes in Aß pattern could be described, allowing separation of patients with pure FTLD from ALS + FTLD. Combination of sAPP and Aß values improves group differentiation. These findings may provide information on pathophysiological processes in the ALS-FTLD disease spectrum and could have impact in neurochemical diagnosis. We propose to expand this study to larger patient groups comprising followed up cases with known neuropathology.

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Abbreviations

Aβ:

Beta-amyloid peptide

sAPP:

Soluble amyloid precursor protein

ALS:

Amyotrophic lateral sclerosis

CON:

Control subjects

CSF:

Cerebrospinal fluid

DI:

Frontal disinhibition

FTD:

Frontotemporal dementia

FTLD:

Frontotemporal lobar degeneration

FTLD-U:

Frontotemporal lobar degeneration with ubiquitin positive and tau-negative inclusions

MND:

Motor neuron disease

SD:

Standard deviation

TDP-43:

TAR-DNA binding protein 43

A + F:

Amyotrophic lateral sclerosis + Frontotemporal lobar degeneration

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Acknowledgments

We thank all physicians notifying suspect cases to our clinic. This project was in part supported by the Landesstiftung Baden-Württemberg (P-LS-Prot/42), the European Commission (cNeupro, NeuroTAS, Anteprion) and the Federal Ministry of Education and Research (01GI0704) and the Academy of Sciences and Humanities, Heidelberg (WIN-Kolleg, to C.A.F.v.A.).

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Authors and Affiliations

  1. Department of Neurology, University of Ulm, Steinhövelstr. 1, 89075, Ulm, Germany

    Petra Steinacker, Corinna Hendrich, Anne-Dorte Sperfeld, Sarah Jesse, Stefan Lehnert, Alice Pabst, Christine A. F. von Arnim, Ingo Uttner, Hayrettin Tumani, Albert Ludolph & Markus Otto

  2. Department of Nuclear Medicine, UZ Leuven, Leuven, Belgium

    Felix M. Mottaghy

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  1. Petra Steinacker
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Correspondence to Markus Otto.

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Steinacker, P., Hendrich, C., Sperfeld, AD. et al. Concentrations of beta-amyloid precursor protein processing products in cerebrospinal fluid of patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration. J Neural Transm 116, 1169–1178 (2009). https://doi.org/10.1007/s00702-009-0271-4

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