Personal
Javier Sáez Valero
Group leader
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Altered molecular mechanism in Alzheimer’s disease and dementia
https://in.umh-csic.es/group3891
- Selective reduction of ADAM10 in brain and cerebrospinal fluid of Alzheimer’s disease patients Gea-González, A., Valle-Pedroso, R., López-Font, I., Zetterberg, H., Blennow, K., Sáez-Valero, J. and García-Ayllón, M.S. Alzheimer’s Research & Therapy. 2026 18, 98 https://doi.org/10.1186/s13195-026-02007-6
- Alterations of NMDAR Subunits in the Cerebrospinal Fluid Across Neurodegenerative and Immunological Disorders. Sergio Escamilla , Rocío Pérez-González, Carmen Márquez-Marco, Elena Camporesi, Gunnar Brinkmalm ,, Alessandro Padovani , Andrea Pilotto , Chiara Tolassi , Davide Arici, Irene Volonghi , Henrik Zetterberg, Kaj Blennow ,Jesús Pérez-Pérez ,, Jaime Kulisevsky , Inmaculada Cuchillo-Ibáñez ,Javier Sáez-Valero. J Neurochem. 2025 169(8): e70192 https://doi.org/10.1111/jnc.70192
- Increased Cerebrospinal Fluid Angiotensin-Converting Enzyme 2 Fragments as a Read-Out of Brain Infection in Patients With COVID-19 Encephalopathy. Matthew P Lennol, María-Salud García-Ayllón, Carlos Avilés-Granados, Chiara Trasciatti, Chiara Tolassi, Virginia Quaresima, Davide Arici, Viviana Cristillo, Irene Volonghi, Francesca Caprioli, Valeria De Giuli, Sara Mariotto, Sergio Ferrari, Gianluigi Zanusso, Nicholas J Ashton, Henrik Zetterberg, Kaj Blennow, Alessandro Padovani, Andrea Pilotto, Javier Sáez-Valero. The Journal of Infectious Diseases. 2025 231(5): e929–e940 https://doi.org/10.1093/infdis/jiaf093
- Risk for COVID-19 Vulnerability in Patients with Inflammatory Bowel Disease: Assessing Alterations in ACE2 and TMPRSS2. Jorge Sáez-Leyva , Matthew P Lennol , Carlos Avilés-Granados,, María-Salud García-Ayllón, Javier Sáez-Valero Biomedicines. 2025 Review; 13(9): 2240 https://doi.org/10.3390/biomedicines13092240
- NMDARs in Alzheimer’s Disease: Between Synaptic and Extrasynaptic Membranes. Sergio Escamilla, Javier Sáez-Valero and Inmaculada Cuchillo-Ibáñez. Int. J. Mol. Sci. 2024 25(18), 10220 https://doi.org/10.3390/ijms251810220
- Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer’s disease patients. Escamilla S, Badillos R, Comella JX, Solé M, Pérez-Otaño I, Sánchez Mut JV, Sáez-Valero J and Cuchillo-Ibáñez I. Alzheimer's & Dementia 2024 1-15 (in press) https://doi.org/10.1002/alz.14125
- ADAM10 Gene Variants in AD Patients and Their Relationship to CSF Protein Levels. Pablo Agüero-Rabes , Julián Pérez-Pérez , Lucía Cremades-Jimeno, María-Salud García-Ayllón , Adriana Gea-González , María José Sainz, Ignacio Mahillo-Fernández , Raquel Téllez , Blanca Cárdaba , Javier Sáez-Valero and Estrella Gómez-Tortosa Int. J. Mol. Sci. 2023 24 (7), 6113 https://doi.org/10.3390/ijms24076113
- BACE2 beyond β-processing of APP, its neuroprotective role in cerebrovascular endothelium. Javier Sáez-Valero, Rocío Pérez-González Journal of Neurochemistry. 2023 166 (6): 887-890 - Editorial https://doi.org/10.1111/jnc.15940
- No evidence for cognitive decline or neurodegeneration in strain-matched Grin3a knockout mice. Remy Verhaeghe, Oscar Elía-Zudaire, Sergio Escamilla, Javier Sáez-Valero, Isabel Pérez-Otaño Alzheimer's & Dementia. 2023 19 (9), pp. 4264 - 4266 https://doi.org/10.1002/alz.13375
- Presenilin 1 Modulates Acetylcholinesterase Trafficking and Maturation. Cortés-Gómez, M.Á., Barberá, V.M., Alom, J., Sáez-Valero, J., García-Ayllón, M.-S. Int J Mol Sci. 2023 24(2): art. 1437 https://doi.org/10.3390/ijms24021437
- Transient Changes in the Plasma of Astrocytic and Neuronal Injury Biomarkers in COVID-19 Patients without Neurological Syndromes. Lennol, M.P.; Ashton, N.J.; Moreno-Pérez, O.; García-Ayllón, M.-S.; Ramos-Rincon, J.-M.; Andrés, M.; León-Ramírez, J.-M.; Boix, V.; Gil, J.; Blennow, K.; et al. Int. J. Mol. Sci. 2023 24(3): 2715 https://doi.org/10.3390/ijms24032715
- Validity of CSF alpha-synuclein to predict psychosis in prodromal Alzheimer’s disease. Sonia Monge-García, María-Salud García-Ayllón, José Sánchez-Payá, Ruth Gasparini-Berenguer, María- Ángeles Cortés-Gómez, Javier Sáez-Valero, José-Antonio Monge-Argilés Front. Neurol. 2023 Sec. Neurological Biomarkers, Volume 14 - 2023 https://doi.org/10.3389/fneur.2023.1124145
- Altered Balance of Reelin Proteolytic Fragments in the Cerebrospinal Fluid of Alzheimer’s Disease Patients. Lopez-Font, I., Lennol, M.P., Iborra-Lazaro, G., Zetterberg, H., Blennow, K., Sáez-Valero, J. Int J Mol Sci . 2022 23 (14): art. 7522 https://doi.org/10.3390/ijms23147522
- Apolipoprotein E imbalance in the cerebrospinal fluid of Alzheimer’s disease patients Matthew Paul Lennol, Irene Sánchez-Domínguez, Inmaculada Cuchillo-Ibañez, Elena Camporesi, Gunnar Brinkmalm, Daniel Alcolea, Juan Fortea, Alberto Lleó, Guadalupe Soria, Fernando Aguado, Henrik Zetterberg, Kaj Blennow & Javier Sáez-Valero Alzheimer's Research & Therapy 2022 14, Article number: 161 (2022) https://doi.org/10.1186/s13195-022-01108-2
- Serum angiotensin-converting enzyme 2 as a potential biomarker for SARS-CoV-2 infection and vaccine efficacy. Lennol, M.P., García-Ayllón, M.-S., Esteban, M., García-Arriaza, J., Sáez-Valero, J. Frontiers in Immunology 2022 13: art 1001951 https://doi.org/10.3389/fimmu.2022.1001951
- Increased P2x2 receptors induced by amyloid-beta peptide participates in the neurotoxicity in alzheimer’s disease Godoy PA, Mennickent D, Cuchillo-Ibáñez I, Ramírez-Molina O, Silva-Grecchi T, Panes-Fernández J, Castro P, Sáez-Valero J, Fuentealba J Biomed Pharmacother 2021 142:111968 https://doi.org/10.1016/j.biopha.2021.111968
- Plasma ACE2 species are differentially altered in COVID-19 patients García-Ayllón MS, Moreno-Pérez O, García-Arriaza J, Ramos-Rincón JM, Cortés-Gómez MÁ, Brinkmalm G, Andrés M, León-Ramírez JM, Boix V, Gil J, Zetterberg H, Esteban M, Merino E, Sáez-Valero J FASEB J 2021 35(8):e21745 https://doi.org/10.1096/fj.202100051R
- Relation between Alpha-Synuclein and Core CSF Biomarkers of Alzheimer’s Disease Monge-García V, García-Ayllón MS, Sáez-Valero J, Sánchez-Payá J, Navarrete-Rueda F, Manzanares-Robles J, Gasparini-Berenguer R, Romero-Lorenzo R, Cortés-Gómez MA, Monge-Argilés JA Medicina (Kaunas) 2021 57(9):954 https://doi.org/10.3390/medicina57090954
- Tau phosphorylation by glycogen synthase kinase 3 beta modulates enzyme acetylcholinesterase expression Cortés-Gómez MÁ, Llorens-Álvarez E, Alom J, Del Ser T, Avila J, Sáez-Valero J, García-Ayllón MS J Neurochem 2021 157(6):2091 https://doi.org/10.1111/jnc.15189
- The apolipoprotein receptor LRP3 compromises APP levels Cuchillo-Ibañez I, Lennol MP, Escamilla S, Mata-Balaguer T, Valverde-Vozmediano L, Lopez-Font I, Ferrer I, Sáez-Valero J Alzheimers Res Ther 2021 13(1):181 https://doi.org/10.1186/s13195-021-00921-5
- a-Secretase nonsense mutation (ADAM10 Tyr167*) in familial Alzheimer’s disease Agüero P, Sainz MJ, García-Ayllón MS, Sáez-Valero J, Téllez R, Guerrero-López R, Pérez-Pérez J, Jiménez-Escrig A, Gómez-Tortosa E Alzheimers Res Ther 2020 12(1):139 https://doi.org/10.1186/s13195-020-00708-0
- Amyloid precursor protein glycosylation is altered in the brain of patients with Alzheimer’s disease Boix CP, Lopez-Font I, Cuchillo-Ibañez I, Sáez-Valero J Alzheimers Res Ther 2020 12(1):96 https://doi.org/10.1186/s13195-020-00664-9
- Elevated Plasma Reelin Levels in Children With Autism Cuchillo-Ibáñez I, Andreo-Lillo P, Pastor-Ferrándiz L, Carratalá-Marco F, Sáez-Valero J Front Psychiatry 2020 11:242 https://doi.org/10.3389/fpsyt.2020.00242
- Characterization of Cerebrospinal Fluid BACE1 Species Lopez-Font I, Boix CP, Zetterberg H, Blennow K, Sáez-Valero J Molecular Neurobiology 2019 56(12):8603 https://doi.org/10.1007/s12035-019-01677-8
- CSF-ApoER2 fragments as a read-out of reelin signaling: Distinct patterns in sporadic and autosomal-dominant Alzheimer disease Lopez-Font I, Iborra-Lazaro G, Sánchez-Valle R, Molinuevo JL, Cuchillo-Ibañez I, Sáez-Valero J Clinica Chimica Acta 2019 490:6 https://doi.org/10.1016/j.cca.2018.12.012
- Decreased circulating ErbB4 ectodomain fragments as a read-out of impaired signaling function in amyotrophic lateral sclerosis Lopez-Font I, Sogorb-Esteve A, Javier-Torrent M, Brinkmalm G, Herrando-Grabulosa M, García-Lareu B, Turon-Sans J, Rojas-García R, Lleó A, Saura CA, Zetterberg H, Blennow K, Bosch A, Navarro X4, Sáez-Valero J Neurobiology of Disease 2019 124:428 https://doi.org/10.1016/j.nbd.2018.12.021
- Measurement of CSF alpha-synuclein improves early differential diagnosis of mild cognitive impairment due to Alzheimer’s disease García-Ayllón MS, Monge-Argilés JA, Monge-García V, Navarrete F, Cortés-Gómez MA, Sánchez-Payá J, Manzanares J, Gasparini-Berenguer R, Leiva-Santana C, Sáez-Valero J Journal of Neurochemistry 2019 150(2):218 https://doi.org/10.1111/jnc.14719
- Pre-analytical stability of novel cerebrospinal fluid biomarkers Willemse EAJ, Vermeiren Y, Garcia-Ayllon MS, Bridel C, De Deyn PP, Engelborghs S, van der Flier WM, Jansen EEW, Lopez-Font IB, Mendes V, Manadas B, de Roeck N, Saez-Valero J, Struys EA, Vanmechelen E, Andreasson U, Teunissen CE Clinica Chimica Acta 2019 497:204 https://doi.org/10.1016/j.cca.2019.07.024
- Decreased generation of C-terminal fragments of ApoER2 and increased reelin expression in Alzheimer’s disease Mata-Balaguer T, Cuchillo-Ibanez I, Calero M, Ferrer I, Saez-Valero J FASEB J 2018 32(7):3536 https://doi.org/10.1096/fj.201700736RR
- Inhibition of gamma-Secretase Leads to an Increase in Presenilin-1 Sogorb-Esteve A, Garcia-Ayllon MS, Llansola M, Felipo V, Blennow K, Saez-Valero J Mol Neurobiol 2018 55(6):5047 https://doi.org/10.1007/s12035-017-0705-1
- Levels of ADAM10 are reduced in Alzheimer’s disease CSF Sogorb-Esteve A, Garcia-Ayllon MS, Gobom J, Alom J, Zetterberg H, Blennow K, Saez-Valero J J Neuroinflammation 2018 15:213 https://doi.org/10.1186/s12974-018-1255-9
- Alterations in the Balance of Amyloid-beta Protein Precursor Species in the Cerebrospinal Fluid of Alzheimer’s Disease Patients Lopez-Font I, Boix CP, Zetterberg H, Blennow K, Saez-Valero J J Alzheimers Dis 2017 57(4):1281 https://doi.org/10.3233/JAD-161275
- C-terminal fragments of the amyloid precursor protein in cerebrospinal fluid as potential biomarkers for Alzheimer disease Garcia-Ayllon MS, Lopez-Font I, Boix CP, Fortea J, Sanchez-Valle R, Lleo A, Molinuevo JL, Zetterberg H, Blennow K, Saez-Valero J Sci Rep 2017 7:2477 https://doi.org/10.1038/s41598-017-02841-7
- HNK-1 Carrier Glycoproteins Are Decreased in the Alzheimer’s Disease Brain Garcia-Ayllon MS, Botella-Lopez A, Cuchillo-Ibañez I, Rabano A, Andreasen N, Blennow K, avila J, Saez-Valero J Mol Neurobiol 2017 54(1):188 https://doi.org/10.1007/s12035-015-9644-x
- Cerebrospinal fluid Presenilin-1 increases at asymptomatic stage in genetically determined Alzheimer’s disease Sogorb-Esteve A, Garcia-Ayllon MS, Fortea J, Sanchez-Valle R, Lleo A, Molinuevo JL, Saez-Valero J Mol Neurodegener 2016 11:66 https://doi.org/10.1186/s13024-016-0131-2
- Increased Expression of Readthrough Acetylcholinesterase Variants in the Brains of Alzheimer’s Disease Patients Campanari ML, Navarrete F, Ginsberg SD, Manzanares J, Saez-Valero J, Garcia-Ayllon MS J Alzheimers Dis 2016 53(3):831 https://doi.org/10.3233/JAD-160220
- Neuromuscular Junction Impairment in Amyotrophic Lateral Sclerosis: Reassessing the Role of Acetylcholinesterase Campanari ML, Garcia-Ayllon MS, Ciura S, Saez-Valero J, Kabashi E Front Mol Neurosci 2016 9:160 https://doi.org/10.3389/fnmol.2016.00160
- Reelin in Alzheimer’s Disease, Increased Levels but Impaired Signaling: When More is Less Cuchillo-Ibañez I, Balmaceda V, Mata-Balaguer T, Lopez-Font I, Saez-Valero J J Alzheimers Dis 2016 52(2):403 https://doi.org/10.3233/JAD-151193
- The beta-amyloid peptide compromises Reelin signaling in Alzheimer’s disease Cuchillo-Ibañez I, Mata-Balaguer T, Balmaceda V, Arranz JJ, Nimpf J, Saez-Valero J Sci Rep 2016 6:31646 https://doi.org/10.1038/srep31646
- Heteromers of amyloid precursor protein in cerebrospinal fluid Cuchillo-Ibañez I, Lopez-Font I, Boix-Amoros A, Brinkmalm G, Blennow K, Molinuevo JL, Saez-Valero J Mol Neurodegener 2015 10:2 https://doi.org/10.1186/1750-1326-10-2
- Transmembrane amyloid-related proteins in CSF as potential biomarkers for Alzheimer’s disease Lopez-Font I, Cuchillo-Ibañez I, Sogorb-Esteve A, Garcia-Ayllon MS, Saez-Valero J Front Neurol 2015 6:UNSP 125 https://doi.org/10.3389/fneur.2015.00125
- Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study Kruse N, Persson S, Alcolea D, Bahl JMC, Baldeiras I,Capello E, Chiasserini D, Garcia-Ayllon MS, Genc S,Gkatzima O, Heegaard NHH Janeiro AM, Saez-Valero J, Struyfs H,Tanassi JT, Zetterberg H, Mollenhauer B Neurobiol Aging 2015 36(9):2587 https://doi.org/10.1016/j.neurobiolaging.2015.05.003
- Acetylcholinesterase Modulates Presenilin-1 Levels and ?-Secretase Activity Campanari ML, Garcia-Ayllon MS, Belbin O, Galceran J, Lleo A, Saez-Valero J J Alzheimer Dis 2014 41(3):911 https://doi.org/10.3233/JAD-140426
- Acetylcholinesterase Protein Level Is Preserved in the Alzheimer’s Brain Campanari ML, Garcia-Ayllon MS, Blazquez-Llorca L, Luk WKW, Tsim K, Saez-Valero J J Mol Neurosci 2014 53(3):446 https://doi.org/10.1007/s12031-013-0183-5
- ApoER2 processing by presenilin-1 modulates reelin expression Balmaceda V, Cuchillo-Ibañez I, Pujadas L, Garcia-Ayllon MS, Saura CA, Nimpf J, Soriano E, Saez-Valero J Faseb J 2014 28(4):1543 https://doi.org/10.1096/fj.13-239350
- Presenilin-1 influences processing of the acetylcholinesterase membrane anchor PRiMA Garcia-Ayllon MS, Campanari ML, Montenegro MF, Cuchillo-Ibañez I, Belbin O, Lleo A, Tsim K, Vidal CJ, Saez-Valero J Neurobiol Aging 2014 35(7):1526 https://doi.org/10.1016/j.neurobiolaging.2014.01.147
- Quantification of the transcripts encoding differentfForms of AChE in various cell types: real-Time PCR coupled with standards in revealing the copy number Bi CW, Luk WK, Campanari ML, Liu YH, Xu L, Lau KM, Xu ML, Choi RC, Saez-Valero J, Tsim KW J Mol Neurosci 2014 53(3):461 https://doi.org/10.1007/s12031-013-0210-6
- Beta-amyloid impairs reelin signaling Cuchillo-Ibañez I, Balmaceda V, Botella-Lopez A, Rabano A, Avila J, Saez-Valero J PLoS One 2013 8(8):UNSP e72297 https://doi.org/10.1371/journal.pone.0072297
- CSF Presenilin-1 complexes are increased in Alzheimer’s disease Garcia-Ayllon MS, Campanari ML, Brinkmalm G, Rabano A, Alom J, Saura CA, Andreasen N, Blennow K, Saez-Valero J Acta Neuropathol 2013 1:46 https://doi.org/10.1186/2051-5960-1-46
- Identification of a 31-bp Deletion in the RELN Gene Causing Lissencephaly with Cerebellar Hypoplasia in Sheep Suarez-Vega A, Gutierrez-Gil B, Cuchillo-Ibañez I, Saez-Valero J, Perez V, Garcia-Gamez E, Benavides J, Arranz JJ PLoS One 2013 8(11):UNSP e81072 https://doi.org/10.1371/journal.pone.0081072
- Altered expression of brain acetylcholinesterase in FTDP-17 human tau transgenic mice Silveyra MX, Garcia-Ayllon MS, de Barreda EG, Small DH, Martinez S, Avila J, Saez-Valero J Neurobiol Aging 2012 33(3):624.e23 https://doi.org/10.1016/j.neurobiolaging.2011.03.006
- Changes in acetylcholinesterase expression are associated with altered presenilin-1 levels Silveyra MX, Garcia-Ayllon MS, Serra-Basante C, Mazzoni V, Garcia-Gutierrez MS, Manzanares J, Culvenor JG, Saez-Valero J Neurobiol Aging 2012 33(3):627.e27 https://doi.org/10.1016/j.neurobiolaging.2011.04.006
- Readthrough Acetylcholinesterase Is Increased in Human Liver Cirrhosis Garcia-Ayllon MS, Millan C, Serra-Basante C, Bataller R, Saez-Valero J PLoS ONE 2012 7(9):e44598 https://doi.org/10.1371/journal.pone.0044598
- Recommendations to standardize preanalytical confounding factors in Alzheimers and Parkinsons disease cerebrospinal fluid biomarkers: An update Del Campo M, Mollenhauer B, Bertolotto A, Engelborghs S, Hampel H, Simonsen AH, Kapaki E, Kruse N, Le Bastard N, Lehmann S, Molinuevo JL, Parnetti L, Perret-Liaudet A, Saez-Valero J, Saka E, Urbani A, Vanmechelen E, Verbeek M, Visser PJ, Teunissen C Biomark Med 2012 6(4):419 https://doi.org/10.2217/BMM.12.46
- Revisiting the Role of Acetylcholinesterase in Alzheimer’s Disease: Cross-Talk with P-tau and beta-Amyloid Garcia-Ayllon MS, Small DH, Avila J, Saez-Valero J Front Mol Neurosci 2011 4:22 https://doi.org/10.3389/fnmol.2011.00022
- Altered Levels of Acetylcholinesterase in Alzheimer Plasma Garcia-Ayllon MS, Riba-Llena I, Serra-Basante C, Alom J, Boopathy R, Saez-Valero J PLoS ONE 2010 5(1):e8701 https://doi.org/10.1371/journal.pone.0008701
- beta-amyloid controls altered Reelin expression and processing in Alzheimer’s disease Botella-Lopez A, Cuchillo-Ibañez I, Cotrufo T, Mok SS, Li QX, Barquero MS, Dierssen M, Soriano E, Saez-Valero J Neurobiol Dis 2010 37(3):682 https://doi.org/10.1016/j.nbd.2009.12.006
Javier Sáez Valero