Journal of Neural Transmission

, Volume 116, Issue 9, pp 1169–1178

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

  • Petra Steinacker
  • Corinna Hendrich
  • Anne-Dorte Sperfeld
  • Sarah Jesse
  • Stefan Lehnert
  • Alice Pabst
  • Christine A. F. von Arnim
  • Felix M. Mottaghy
  • Ingo Uttner
  • Hayrettin Tumani
  • Albert Ludolph
  • Markus Otto
Dementias - Original Article

DOI: 10.1007/s00702-009-0271-4

Cite this article as:
Steinacker, P., Hendrich, C., Sperfeld, AD. et al. J Neural Transm (2009) 116: 1169. doi:10.1007/s00702-009-0271-4

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.

Keywords

Frontotemporal lobar degenerationAmyotrophic lateral sclerosisBeta-amyloid precursor proteinBeta-amyloid peptidesDifferential diagnosis

Abbreviations

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

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Petra Steinacker
    • 1
  • Corinna Hendrich
    • 1
  • Anne-Dorte Sperfeld
    • 1
  • Sarah Jesse
    • 1
  • Stefan Lehnert
    • 1
  • Alice Pabst
    • 1
  • Christine A. F. von Arnim
    • 1
  • Felix M. Mottaghy
    • 2
  • Ingo Uttner
    • 1
  • Hayrettin Tumani
    • 1
  • Albert Ludolph
    • 1
  • Markus Otto
    • 1
  1. 1.Department of NeurologyUniversity of UlmUlmGermany
  2. 2.Department of Nuclear MedicineUZ LeuvenLeuvenBelgium