Department: Bioquímica y Biología Molecular

Research Unit: Instituto de Neurociencias

Research Gate:

ORCID: 0000-0001-7480-320X / Researcher ID: K-5756-2014

Instituto Neurociencias: https://in.umh-csic.es/es/grupos/mecanismos-moleculares-alterados-en-la-enfermedad-de-alzheimer-y-otras-demencias/

CIBERNED: https://www.ciberned.es/grupos/grupo-de-investigacion?id=28584

Google academic: https://scholar.google.es/citations?view_op=list_works&hl=es&user=GcD48VcAAAAJ

Research Fields: 

We aim to clarify the pathological mechanisms behind Alzheimer’s disease but also to define potential diagnostic tools and/or processes with therapeutic relevance. We aim to identify biomarkers that serve as a read-out of impaired brain function. For this reason we validate potential biomarkers in cellular models; with an extensive experience in modeling the disease condition in primary cultures and cell line; now extending this experience to iPS cells.

Our expertise comprises i) biochemical characterization of post-translational modifications for brain proteins, including glycosylation and phosphorylation analysis, as characterization of proteolytic processing; ii) characterization of ligand-receptor interaction associated to signaling pathways; iii) assessment of sustained inhibition of key enzymes such as secretases and acetylcholinesterase.

Among the studies by our group, there are i) cross-talk of Alzheimer’s key proteins Aβ and P-tau, role for the apolipoprotein (apoE). An impaired apoE signaling (triggered by β-amyloid) through receptor interaction will result in compromised function. Characterization of glycosylation, oligomerization and fragmentation; ii) Development of new CSF biomarkers, evaluating the PTM, which improve sensitivity and specificity of the biomarkers. We also identify in the CSF several secretases and APP proteolytic fragments; iii) To explore extracellular vesicles (EVs) as a source of AD biomarkers by characterizing EV subpopulations in brain tissues, CSF and blood iv) We have developed a new protocol to isolate synaptic and extrasynaptic membranes for characterizing altered distribution of synaptic proteins.

The research line in COVID-19 focus is focus in the host coronavirus receptor ACE2 and proteases related with SARS-CoV-2 entry.

Representative Publications:

• Avilés-Granados C, Gea-González A, Sáez-Leyva J, Perez SE, Mufson EJ, Granholm AC, Carmona-Iragui M, Zetterberg H, Blennow K, Fortea J, García-Ayllón MS, Sáez-Valero J. Acta Neuropathol Commun. Cerebrospinal fluid and frontal cortex TMPRSS2 and ACE2 protein levels differ in Down syndrome and Alzheimer’s disease. 2026 Apr 9. doi: 10.1186/s40478-026-02289-9.
• Escamilla S, Badillos R, Comella JX, Solé M, Pérez-Otaño I, Sánchez Mut JV, Sáez-Valero J, Cuchillo-Ibáñez I. Synaptic and extrasynaptic distribution of NMDA receptors in cortex of Alzheimer’s disease patients. Alzheimers Dement 2024, 20:8231-8245.
• Lennol MP, Sánchez-Domínguez I, Cuchillo-Ibañez I,Camporesi E, Brinkmalm G, Alcolea D, Fortea J, Lleó A, Soria G, Aguado F, Zetterberg H, Blennow K, Sáez-Valero. Apolipoprotein E imbalance in the cerebrospinal fluid of Alzheimer’s disease patients. Alzheimers Res Ther 2022, 14:161.
• Boix CP, Lopez-Font I, Cuchillo-Ibañez I, Sáez-Valero J. Amyloid precursor protein glycosylation is altered in the brain of patients with Alzheimer’s disease. Alzheimers Res Ther 2020, 12:96.
• Sogorb-Esteve A, García-Ayllón MS, Fortea J, Sánchez-Valle R, Lleó A, Molinuevo JL, Sáez-Valero J. Cerebrospinal fluid Presenilin-1 increases at asymptomatic stage in genetically determined Alzheimer’s disease. Mol Neurodegener 2016, 11:66.
• Cuchillo-Ibañez I, López-Font I, Boix-Amorós A, Brinkmalm G, Blennow K, Molinuevo JL, Sáez-Valero J. Heteromers of amyloid precursor protein in cerebrospinal fluid. Mol Neurodegener 2015; 10:2.
• García-Ayllón MS, Caulí O, Silveyra MX, Rodrigo R, Candela A, Compañ A, Jover R, Pérez-Mateo M, Martínez S, Felipo V, Sáez-Valero J. Brain cholinergic impairment in liver failure. Brain 2008; 131:2946.
• Botella-López A, Burgaya F, Gavín R, García-Ayllón MS, Gómez-Tortosa E, Peña-Casanova J, Ureña JM, del Río JA, Blesa R, Soriano E, Sáez-Valero J. Reelin expression and glycosylation patterns are altered in Alzheimer’s disease. Proc Natl Acad Sci USA 2006; 103:5573.
• García-Ayllón MS, Silveyra MX, Candela A, Compañ A, Clària J, Jover R, Pérez-Mateo M, Felipo V, Martínez S, Galcerán J, Sáez-Valero J. Changes in liver and plasma acetylcholinesterase of rats with bile duct ligation. Hepatology 2006; 43:444.
• Sáez-Valero J, Sberna G, McLean CA, Masters CL, Small DH. Glycosylation of acetylcholinesterase as diagnostic marker for Alzheimer’s disease. Lancet 1997; 350: 929.

Patents and Available Technologies: 

1. TITLE: Method and diagnostic kit for Alzheimer’s disease based on the detection of apolipoprotein E. INVENTORS: Sáez-Valero J, Lennol M.P., Cuchillo-Ibañez I. P202230224. PRIORITY COUNTRY: Spain. PRIORITY DATE: 17/03/2022. ENTITY: Universidad Miguel Hernández de Elche/CIBERNED/CSIC
2. TITLE: Analysis of sAPP glycoforms as a biomarker for Alzheimer’s disease. INVENTORS: Sáez-Valero J, Lopez-Font IB, Cuchillo-Ibañez I, Boix-Rodriguez CP. P202030671. PRIORITY COUNTRY: Spain. PRIORITY DATE: 01/07/2020. ENTITY: Universidad Miguel Hernández de Elche/CIBERNED/CSIC.