title: Correlations between soluble α/β forms of amyloid precursor protein and Aβ38, 40, and 42 in human cerebrospinal fluid.
abstract: Cerebrospinal fluid (CSF) biomarkers are now widely used for diagnosis of Alzheimer disease (AD) in atypical clinical forms, for differential and early diagnosis, or for stratification of patients in clinical trials. Among these biomarkers, different forms of amyloid peptides (Aβ) produced by the cleavage of a transmembrane precursor protein called APP (amyloid precursor protein) have a major role. Aβ peptides exist in different length the most common ones having 40 (Aβ40), 42 (Aβ42), or 38 (Aβ38) amino acids in length. APP processing by gamma-secretase releases also an amino-terminal secreted fragment called sAβPP-beta while an alternative nonamyloidogenic cleavage of APP, through an alpha-secretase, liberates another fragment called sAβPP-alpha. To decipher the molecular and pathological mechanisms leading to the production and the detection of these entities is essential for the comprehension and the prevention of AD. In this report, we present the results of the multiplex measurement of CSF Aβ38, Aβ40, Aβ42, sAβPP-alpha, and sAβPP-beta in 60 patients mostly with dementia eventually segregated between neurochemical dementia diagnostic (NDD) positive and negative groups. The NDD classification was based on our routine Tau, P-tau(181), and Aβ(42) cutoff values. We confirmed previous findings regarding the correlation between sAβPP-alpha and sAβPP-beta, as well as the potential interest of these new biomarkers. We also studied the correlation between sAβPPs and Aβ peptides, as well as between Aβ peptides themselves. We observed a strong correlation between Aβ38 and sAβPP-beta which suggested that the production of this peptide was in direct relation with β secretase activities. We also reported a strong correlation between Aβ38 and Aβ40, while Aβ42 was correlated to these fragments only in nonpathological situations. These results enlighten the complex relationships between these molecular markers in both physiological and pathological situations. Our results are important for the further use of these analytes for AD diagnosis as well as for validating the cell biological hypotheses of APP processing and Aβ fragment production.
authors: Centre Mémoire Recherche Ressources Montpellier, Hôpital Gui de Chauliac, CHU de Montpellier, 34025 Montpellier cedex 5, France. a-gabelle@chu-montpellier.fr
authors: Audrey
authors: A
authors: Gabelle
authors: Stéphane
authors: S
authors: Roche
authors: Christian
authors: C
authors: Gény
authors: Karim
authors: K
authors: Bennys
authors: Pierre
authors: P
authors: Labauge
authors: Yannick
authors: Y
authors: Tholance
authors: Isabelle
authors: I
authors: Quadrio
authors: Laurent
authors: L
authors: Tiers
authors: Baptiste
authors: B
authors: Gor
authors: Chloé
authors: C
authors: Chaulet
authors: Alain
authors: A
authors: Vighetto
authors: Bernard
authors: B
authors: Croisile
authors: Pierre
authors: P
authors: Krolak-Salmon
authors: Jacques
authors: J
authors: Touchon
authors: Armand
authors: A
authors: Perret-Liaudet
authors: Sylvain
authors: S
authors: Lehmann
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D010446:Peptide Fragments