title: Soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis.
abstract: BACKGROUND
  Biomarkers of disease progression in amyotrophic lateral sclerosis (ALS) could support the identification of beneficial drugs in clinical trials. We aimed to test whether soluble fragments of beta-amyloid precursor protein (sAPPα and sAPPß) correlated with clinical subtypes of ALS and were of prognostic value.
  
  
  RESULTS
  In a cross-sectional study including patients with ALS (N = 68) with clinical follow-up data over 6 months, Parkinson's disease (PD, N = 20), and age-matched controls (N = 40), cerebrospinal fluid (CSF) levels of sAPPα a, sAPPß and neurofilaments (NfH(SMI35)) were measured by multiplex assay, Progranulin by ELISA. CSF sAPPα and sAPPß levels were lower in ALS with a rapidly-progressive disease course (p = 0.03, and p = 0.02) and with longer disease duration (p = 0.01 and p = 0.01, respectively). CSF NfH(SMI35) was elevated in ALS compared to PD and controls, with highest concentrations found in patients with rapid disease progression (p<0.01). High CSF NfH(SMI3) was linked to low CSF sAPPα and sAPPß (p = 0.001, and p = 0.007, respectively). The ratios CSF NfH(SMI35)/CSF sAPPα,-ß were elevated in patients with fast progression of disease (p = 0.002 each). CSF Progranulin decreased with ongoing disease (p = 0.04).
  
  
  CONCLUSIONS
  This study provides new CSF candidate markers associated with progression of disease in ALS. The data suggest that a deficiency of cellular neuroprotective mechanisms (decrease of sAPP) is linked to progressive neuro-axonal damage (increase of NfH(SMI35)) and to progression of disease.
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Steinacker
authors.forename: Lubin
authors.initials: L
authors.lastname: Fang
authors.forename: Jens
authors.initials: J
authors.lastname: Kuhle
authors.forename: Axel
authors.initials: A
authors.lastname: Petzold
authors.forename: Hayrettin
authors.initials: H
authors.lastname: Tumani
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.forename: Markus
authors.initials: M
authors.lastname: Otto
authors.forename: Johannes
authors.initials: J
authors.lastname: Brettschneider
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid*; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D010300:Parkinson Disease / Q000134:cerebrospinal fluid / Q000473:pathology; D011379:Prognosis; D000077153:Progranulins; D020033:Protein Isoforms / Q000134:cerebrospinal fluid; D012372:ROC Curve; D055815:Young Adult
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D016900:Neurofilament Proteins; D000077153:Progranulins; D020033:Protein Isoforms; C051774:neurofilament protein H