title: CSF Presenilin-1 complexes are increased in Alzheimer's disease.
abstract: BACKGROUND
  Presenilin-1 (PS1) is the active component of the amyloid precursor protein cleaving γ-secretase complex. PS1 protein is a transmembrane protein containing multiple hydrophobic regions which presence in cerebrospinal fluid (CSF) has not been measured to date. This study assesses whether PS1 and other components of the γ-secretase complex are present in CSF.
  
  
  RESULTS
  Here, we show that PS1 is present in ventricular post-mortem and lumbar ante-mortem CSF, and plasma as 100-150-kDa hetero-complexes containing both the N- and C-terminal fragments (NTF and CTF) of the protein. Immunoprecipitation and immunoblotting with different antibodies confirmed the identity of the PS1 species. The γ-secretase components, APH-1 (anterior pharynx-defective 1) and PEN-2 (presenilin enhancer 2), as well as presenilin-2 (PS2) fragments, co-exist within these CSF complexes, while nicastrin is not detected. These CSF-PS1 complexes differ from active γ-secretase membrane-complexes, and may represent nonspecific aggregation of the PS1 protein. Levels of PS1 complexes are increased in CSF samples from autopsy-confirmed Alzheimer's disease (AD) cases and were found to be more stable than complexes in CSF from control subjects. Despite similar levels of total PS1 in CSF from probable AD patients and cognitively normal subjects, an increased proportion of highly stable PS1 complexes were observed in AD CSF.
  
  
  CONCLUSIONS
  Our data suggest that fragments of the PS1 protein present in CSF as complexes may be useful as a biomarker for AD.
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Av, Ramón y Cajal s/n, Sant Joan d'Alacant E-03550, Spain. j.saez@umh.es.
authors.forename: María-Salud
authors.initials: MS
authors.lastname: García-Ayllón
authors.forename: María-Letizia
authors.initials: ML
authors.lastname: Campanari
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brinkmalm
authors.forename: Alberto
authors.initials: A
authors.lastname: Rábano
authors.forename: Jordi
authors.initials: J
authors.lastname: Alom
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Saura
authors.forename: Niels
authors.initials: N
authors.lastname: Andreasen
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Javier
authors.initials: J
authors.lastname: Sáez-Valero
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D053829:Amyloid Precursor Protein Secretases / Q000134:cerebrospinal fluid; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D010450:Endopeptidases; D005260:Female; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008159:Lumbar Vertebrae; D008297:Male; D008565:Membrane Proteins / Q000134:cerebrospinal fluid; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000134:cerebrospinal fluid; D053764:Presenilin-1 / Q000097:blood / Q000134:cerebrospinal fluid* / Q000235:genetics
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C469349:PSENEN protein, human; D053764:Presenilin-1; C580804:presenilin 1, mouse; C475154:APH1A protein, human; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D010447:Peptide Hydrolases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human