title: Transmembrane Amyloid-Related Proteins in CSF as Potential Biomarkers for Alzheimer's Disease.
abstract: In the continuing search for new cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD), reasonable candidates are the secretase enzymes involved in the processing of the amyloid precursor protein (APP), as well as the large proteolytic cleavage fragments sAPPα and sAPPβ. The enzymatic activities of some of these secretases, such as BACE1 and TACE, have been investigated as potential AD biomarkers, and it has been assumed that these activities present in human CSF result from the soluble truncated forms of the membrane-bound enzymes. However, we and others recently identified soluble forms of BACE1 and APP in CSF containing the intracellular domains, as well as the multi-pass transmembrane presenilin-1 (PS1) and other subunits of γ-secretase. We also review recent findings that suggest that most of these soluble transmembrane proteins could display self-association properties based on hydrophobic and/or ionic interactions leading to the formation of heteromeric complexes. The oligomerization state of these potential new biomarkers needs to be taken into consideration for assessing their real potential as CSF biomarkers for AD by adequate molecular tools.
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC , Sant Joan d'Alacant , Spain ; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) , Sant Joan d'Alacant , Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Lopez-Font
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC , Sant Joan d'Alacant , Spain ; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) , Sant Joan d'Alacant , Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Cuchillo-Ibañez
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC , Sant Joan d'Alacant , Spain ; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) , Sant Joan d'Alacant , Spain.
authors.forename: Aitana
authors.initials: A
authors.lastname: Sogorb-Esteve
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC , Sant Joan d'Alacant , Spain ; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) , Sant Joan d'Alacant , Spain ; Unidad de Investigación, Fundación para el Fomento de la Investigación Sanitaria Biomédica de la Comunidad Valenciana (FISABIO), Hospital General Universitario de Elche , Elche , Spain.
authors.forename: María-Salud
authors.initials: MS
authors.lastname: García-Ayllón
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC , Sant Joan d'Alacant , Spain ; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) , Sant Joan d'Alacant , Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Sáez-Valero
keywords: Alzheimer’s disease; BACE1; TACE; cerebrospinal fluid; presenilin-1; soluble amyloid precursor protein