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Research Group
Altered molecular mechanism in Alzheimer’s disease and dementia
Unit Unit Molecular Neurobiology »

Principal Investigator Ph.D. Investigator Graduate students / Research Assistant Technician
Research Fields
Our aim in the IN is to introduce a line of research into Alzheimer’s disease (AD) and dementia that originated from a basic point of view but that was relevant to the development of clinical-diagnostic applications. Therefore, the translational benefits of our research lie in the fact that we not only aim to clarify the pathological mechanisms behind these diseases, but also to define potential diagnostic tools and/or processes with therapeutic relevance.

In recent years, we have been involved in studying how β-amyloid influences the expression of acetylcholinesterase (AChE, a key enzyme of the cholinergic system). In addition, we have described for the first time a direct association between presenilin 1 (PS1, a key enzyme in the proteolitic processing of amyloid protein precursor) and AChE, which may be relevant for the pathological progress of dementia and the design of therapeutic strategies.

In the last few years, we have described an altered expression and glycosylation patterns of the glycoprotein Reelin in AD. Reelin is a signaling protein that modulates synaptic function and plasticity in the mature brain, thereby favoring memory formation. Our effort is to demonstrate a novel a novel mechanism by which β-amyloid regulates Reelin expression, thereby influencing its signaling cascade that ultimately controls tau phosphorylation.

Furthermore, we evaluate the diagnostic potential and methodological approaches for analysis of particular glycoforms of proteins, which improve sensitivity and specificity of the biomarkers. We also develop assays to identify secretase-related proteins, related with β-amyloid metabolism, in the cerebrospinal fluid.


Representative Publications

Cuchillo-Ibañez I. , Lopez-Font I, Boix-Amorós A, Brinkmalm G, Blennow K, Molinuevo JL, Sáez-Valero J. " Heteromers of amyloid precursor protein in cerebrospinal fluid. " Mol Neurodegener . 10 , 2 - 2 ( 2015 )

Balmaceda V. , Cuchillo-Ibáñez I, Pujadas L, García-Ayllón MS, Saura CA, Nimpf J, Soriano E, Sáez-Valero J. " ApoER2 processing by presenilin-1 modulates reelin expression. " FASEB J . 28 , 1543 - 1554 ( 2014 )

Silveyra MX. , García-Ayllón MS, Serra-Basante C, Mazzoni V, García-Gutierrez MS, Manzanares J, Culvenor JG, Sáez-Valero J. " Changes in acetylcholinesterase expression are associated with altered presenilin-1 levels. " Neurobiol Aging . 33 , 627.e27 - 627.e37 ( 2012 )

Garcia-Ayllón MS. , Cauli 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 . 131 , 2946 - 2956 ( 2008 )

Botella-Lopez A. , Burgaya, F; Gavin, R; Garcia-Ayllon, MS; Gomez-Tortosa, E; Peña-Casanova, J; Ureña, JM; Del Rio, JA; Blesa, R; Soriano, E; Saez-Valero, J. " Reelin expression and glycosylation patterns are altered in Alzheimer's disease. " Proc Natl Acad Sci USA . 103 , 5573 - 5578 ( 2006 )
CSIC-UMH
 
 
Consejo Superior de Investigaciones Científicas
Universidad Miguel Hernández

Campus de San Juan | Sant Joan d’Alacant
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