CO18: Neurodegeneration and Alzheimer's disease (NeurAlz)

The NeurAlz group works on Alzheimer's disease and on mechanisms involved in the deposition and elimination of beta-amyloid. In recent years we have focused on studying the role of metabolic disorders, and especially type 2 diabetes mellitus, in the development and evolution of Alzheimer's disease and vascular dementia. For this we have different mixed models that we have developed and characterized in our laboratory. At the same time, we have explored different therapeutic alternatives focused on metabolic control. In our studies we use sophisticated neuroimaging techniques such as in vivo and real-time multiphoton microscopy.

• Mónica García Alloza:
• E-mail: monica.garcia@uca.es.
• ORCID: 0000-0003-1610-4114.

• Type 2 diabetes mellitus, vascular dementia and Alzheimer's disease: interrelation and mechanisms involved.
• Alzheimer's disease and type 2 diabetes mellitus: and therapeutic considerations.
• Central complications in children of diabetic mothers: therapeutic considerations.
• Mechanisms of beta-amyloid deposition in mouse models of Alzheimer's disease.
• Characterization of experimental models of intraventricular hemorrhage in the preterm newborn.
• Therapeutic alternatives for intraventricular hemorrhage in the preterm newborn.
• Biochemical and functional markers of hypoxic-ischemic damage in the newborn.

Alzheimer Vascular dementia Mellitus diabetes Intraventricular hemorrhage Multiphoton microscopy Hypoxic-ischemic damage Preterm newborn

• Principal Investigators:
  • Mónica García Alloza (PI).
• Investigators:
  • Gloria Baena Nieto.
  • Carmen Infante García.
  • Ángel del Marco.
  • Carmen Hierro Bujalance.
  • María José Carranza Naval.
  • Pilar Alves.
  • Isabel Atienza Navarro.
  • María Vargas Soria.

• Comisión Europea. H2020-SC1-201.Grant Agreement Number 847749 PI: Mónica García Alloza Investigadores colaboradores del grupo de investigación: Rafael Simó (Hospital Vall d´hebron).Retinal and COGnitive dySfunction in type 2 diabetes: unraveling the common pathways.

• Ministerio de Ciencia, Innovación y Universidades,PID Modalidades Retos (RTI) y Generación de Conocimiento (PGC) PID2020-115499RB-I00 PI: Mónica García Alloza.Complicaciones tempranas en la enfermedad de Alzheimer y en diabetes mellitus tipo 2: implicaciones farmacológicas.
• Ministerio de Ciencia, Innovación y Universidades, Proyectos Explora Ciencia y Explora Tecnología 2017: PID2020-115499RB-I00 PI: Mónica García Alloza. Diabetes mellitus tipo 2: marcadores de daño central in vivo y en tiempo real.
• Ministerio de Economía y Competitividad (MINECO), Agencia Estatal de Investigación, Programa Estatal de I+D+i Orientada a los Retos de la Sociedad BFU2016-75038-R PI: Mónica García Alloza. Enfermedad de ALzheimer, demencia vascular y Diabetes mellitus tipo 2: interrelación y consideraciones terapéuticas.

• Junta de Andalucia. PAIDI 2020 PI: Mónica García Alloza "Diabetes y Enfermedad de ALzheimer: implicaciones en reTina y cErebro (DELETE)".
• Iniciativa Territorial Integrada (ITI) 2014-2020 para la provincia de Cádiz, por la Consejería de Salud y por el Fondo Europeo de Desarrollo Regional PI-0008-2017 PI: Mónica García Alloza "Enfermedad de Alzheimer, prediabetes y diabetes mellitus tipo 2: modelos preclínicos y consideraciones translacionales".

• Plan Inibica. LI19/11IN-CO34 PI: Mónica García Alloza e Isabel Benavente Fernández “Daño cerebral en el recién nacido PREtérmino: MArcadores y consideraciones translacionales (PREMATRANS)”.
• Universidad de Cádiz.FEDER SOL-201800107189-TRA. PI: Mónica García Alloza e Isabel Benavente Fernández “Marcadores de Daño Central en Recién Nacido Pretérmino y Consideraciones Tererapéuticas (Preter)”.

1. Authors: Carranza-Naval MJ, Del Marco A, Hierro-Bujalance C, Alves-Martinez P, Infante-Garcia C, Vargas-Soria M, Herrera M, Barba-Cordoba B, Atienza-Navarro I, Lubian-Lopez S, Garcia-Alloza M. Liraglutide Reduces Vascular Damage, Neuronal Loss, and Cognitive Impairment in a Mixed Murine Model of Alzheimer's Disease and Type 2 Diabetes. Front Aging Neurosci. 2021 Dec 16;13:741923. doi:10.3389/fnagi.2021.741923. eCollection 2021. FI: 5.87 1st quartile (Neurosciences) CO20.
2. Authors: *Little K, Llorián-Salvador M, Scullion S, Hernández C, Simó-Servat O, Del Marco A, Bosma E, Vargas-Soria M, Carranza-Naval MJ, Van Bergen T, Galbiati S, Viganò I, Musi CA, Schlingemann R, Feyen J, Borsello T, Zerbini G, Klaassen I, Garcia-Alloza M, Simó R, Stitt AW; RECOGNISED consortium (GA 847749). Common pathways in dementia and diabetic retinopathy: understanding the mechanisms of diabetes-related cognitive decline. Trends Endocrinol Metab. 2022 Jan;33(1):50-71. doi: 10.1016/j.tem.2021.10.008. Epub 2021 Nov 15. FI: 12.05. 1st decile (Endocrinology and Metabolism).
3. Authors: Garcia-Alloza M, Bacskai BJ, Calvo-Rodriguez M. Mitochondria-ER contacts and glucose: the powerhouse of Alzheimer's disease? Cell Calcium. 2021 Jun 12;97:102434. doi: 10.1016/j.ceca.2021.102434. Online ahead of print. FI: 6.81. 1st quartile (Cell Biology).
4. Authors: Vargas-Soria M, Carranza-Naval MJ, Del Marco A, Garcia-Alloza M. Role of liraglutide in Alzheimer's disease pathology. Alzheimers Res Ther. 2021 Jun 12;13(1):112. doi: 10.1186/s13195-021-00853-0. FI: 6.98. 1st decile (Clinical Neurology).
5. Authors: Carranza-Naval MJ, argas-Soria M, Hierro-Bujalance C, Baena-Nieto G, Garcia-Alloza M, Infante-Garcia C, Del Marco A. Alzheimer's Disease nd Diabetes: Role of Diet, Microbiota and Inflammation in Preclinical Models. Biomolecules. 2021 Feb 10;11(2):262. doi: 10.3390/biom11020262. FI: 4.87. 2º quartile (Biochemistry and Molecular Biology).

• Publications in collaboration with clinical-basic groups:
1. Authors: Carranza-Naval MJ, Del Marco A, Hierro-Bujalance C, Alves-Martinez P, Infante-Garcia C, Vargas-Soria M, Herrera M, Barba-Cordoba B, Atienza-Navarro I, Lubian-Lopez S, Garcia-Alloza M. Liraglutide Reduces Vascular Damage, Neuronal Loss, and Cognitive Impairment in a Mixed Murine Model of Alzheimer's Disease and Type 2 Diabetes. Front Aging Neurosci. 2021 Dec 16;13:741923. doi:10.3389/fnagi.2021.741923. eCollection 2021. FI: 5.87 1st quartile (Neurosciences) CO20.

1. Authors: Domínguez-García S, Gómez-Oliva R, Geribaldi-Doldán N, Hierro-Bujalance C, Sendra M, Ruiz FA, Carrascal L, Macías-Sánchez AJ, Verástegui C, Hernández-Galán R, García- Alloza M, Nunez-Abades P, Castro C. Effects of classical PKC activation on hippocampal neurogenesis and cognitive performance: mechanism of action.. Neuropsychopharmacology. Epub 2020 Dec 17. FI: 7.85 21 May; 46(6):1207-1219. doi: 10.1038/s41386-020-00934-. 1st decile (Pharmacology and Pharmacy) CO5.
2. Authors: Infante-Garcia C, Garcia-Alloza M. Title: Review of the Effect of Natural Compounds and Extracts on Neurodegeneration in Animal Models of Diabetes Mellitus. Journal: Int J Mol Sci. Year, volume, first and last pages: en prensa. Quartile/Decile in the year of publication: Second quartile (Neurosciences).
3. Authors: Benavente-Fernandez F, Ramos-Rodriguez JJ, Infante-Garcia C, Jimenez-Gomez G, Lechuga-Sancho A, Lubian-Lopez S, Monica Garcia-Alloza M. Altered plasma-type gelsolin and amyloid-β in neonates with hypoxic-ischaemic encephalopathy under therapeutic hypothermia. Journal: Journal of Cerebral Blood Flow Metabolism. Year, volume, first and last pages: en prensa. Impact factor: 5.08. Quartile/Decile in the year of publication: First quartile (Neurosciences).

1. Authors: Hierro-Bujalance C, Bacskai BJ, Garcia-Alloza M. Title: In Vivo Imaging of Microglia With Multiphoton Microscopy. Journal: Front Aging Neurosci. Year, volume, first and last pages: 2018 Jul. 19;10:218. doi: 10.3389/fnagi.2018.00218. eCollection 2018. Impact factor: 3.6. Quartile/Decile in the year of publication: Second quartile (Neurosciences).
2. Authors: Segado-Arenas A, Infante-Garcia C, Benavente-Fernandez I, Sanchez-Sotano D, Ramos-Rodriguez JJ, Alonso-Ojembarrena A, Lubian-Lopez S, Garcia-Alloza M. Title: Cognitive impairment, central and peripheral alterations in a murine model of intraventricular hemorrhage in the preterm newborn and in patients Journal: Molecular Neurobiology. Year, volume, first and last pages: 2018. Jun;55(6):4896-4910. Impact factor: 4.58. Quartile/Decile in the year of publication: First quartile (Neurosciences).

1. Authors: Infante-Garcia C, Ramos-Rodriguez JJ, Marin-Zambrana Y, Fernandez-Ponce MT, Casas L, Mantell C,Garcia-Alloza M. Title: Mango leaf extract improves central pathology and cognitive impairment in a type 2 diabetes mouse model. Journal: Brain Pathology. Year, volume, first and last pages: 2017, 27(4):499-507. Impact factor: 6. 2. Quartile/Decile in the year of publication: First decile (Pathology).
2. Authors: Infante-Garcia C, Ramos-Rodriguez JJ, Delgado-Olmos I, Gamero-Carrasco C, Fernandez-Ponce MT, Casas L,Mantell C, Garcia-Alloza M. Title: Long-Term Mangiferin Extract Treatment Improves Central Pathology and Cognitive Deficits in APP/PS1 Mice. Journal: Molecular Neurobiology. Year, volume, first and last pages: 2017, 54(6):4696-4704. Impact factor: 5.07. Quartile/Decile in the year of publication: First quartile (Neurosciences).
3. Authors: Ramos-Rodriguez JJ, Spires-Jones T, Pooler AM, Lechuga-Sancho AM, Bacskai BJ, Garcia-Alloza M. Title: Progressive Neuronal Pathology and Synaptic Loss Induced by Prediabetes and Type 2 Diabetes in a Mouse Model of Alzheimer's Disease. Journal: Molecular Neurobiology. Year, volume, first and last pages: 2017, 54(5):3428-3438. Impact factor: 5.07. Quartile/Decile in the year of publication: First quartile (Neurosciences).
4. Authors: Baena-Nieto G, Lomas-Romero IM, Mateos RM, Leal-Cosme N, Perez-Arana G, Aguilar-Diosdado M, Segundo C, Lechuga-Sancho AM. Title: Ghrelin mitigates β-cell mass loss during insulitis in an animal model of autoimmune diabetes mellitus, the BioBreeding/Worcester rat. Journal: Diabetes Metab Res Rev. Year, volume, first and last pages: 2017 Jan;33(1). Impact factor: 3.9. Quartile/Decile in the year of publication: Second quartile (Endocrinology and Metabolism).
5. Authors: Infante-Garcia C, Ramos-Rodriguez JJ, Hierro-Bujalance C, Ortegon E, Pickett E, Jackson R, Hernandez-Pacho F, Spires-Jones T, Garcia-Alloza M. Title: Antidiabetic Polypill Improves Central Pathology and Cognitive Impairment in a Mixed Model of Alzheimer's Disease and Type 2 Diabetes. Journal: Mol Neurobiol. Year, volume, first and last pages: en prensa. Impact factor: 4.58. Quartile/Decile in the year of publication: First quartile (Neurosciences).
6. Authors: Ramos-Rodriguez JJ, Sanchez-Sotano D, Doblas-Marquez A, Infante-Garcia C, Lubian-Lopez S, Garcia-AllozaM. Title: Intranasal Insulin reverts central pathology and cognitive impairment in diabetic mother offspring Journal: Molecular Neurodegeneration. Year, volume, first and last pages: en prensa. Impact factor: 6.25. Quartile/Decile in the year of publication: First decile (Neurosciences).

1. Authors: Jackson RJ, Rudinskiy N, Herrmann AG, Croft S, Kim JM, Petrova V, Ramos-Rodiguez JJ, Pitstick R, Wegmann S, Garcia-Alloza M, Carlson GA, Hyman BT, Spires-Jones TL. Title: Human tau increases amyloid beta plaque size bot not amyloid beta-mediated synaptse loss in a novel mouse model of Alzheimer ́s disease. Journal: Eur. J. Neurosciences. Year, volume, first and last pages: 2016:44(12):3056-3066. Impact factor: 3.2. Quartile/Decile in the year of publication: Second quartile (Neurosciences).
2. Authors: Infante-Garcia C, Ramos-Rodriguez JJ, Galindo-Gonzalez L, Garcia-Alloza M. Title: Long-term central pathology and cognitive impairment are exacerbated in a mixed model of Alzheimer's disease and type 2 diabetes. Journal: Psychoneuroendocrinology. Year, volume, first and last pages: 2016; 65:15-25. Impact factor: 4.78. Quartile/Decile in the year of publication: First quartile (Psychiatry).

1. Authors: Ramos-Rodriguez JJ, Jimenez-Palomares M, Murillo-Carretero MI, Infante-Garcia C, Berrocoso E, Hernandez-Pacho F, Lechuga-Sancho AM, Cozar-Castellano I, Garcia-Alloza M. Title: Central vascular disease and exacerbated pathology in a mixed model of type 2 diabetes and Alzheimer's disease. Journal: Psychoneuroendocrinology. Year, volume, first and last pages: 2015 Dec;62:69-79. Impact factor: 5.70. Quartile/Decile in the year of publication: First quartile (Psychiatry).
2. Authors: Ramos-Rodriguez JJ, Infante-Garcia C, Galindo-Gonzalez L, Garcia-Molina Y, Lechuga-Sancho A, Garcia-AllozaM. Title: Increased Spontaneous Central Bleeding and Cognition Impairment in APP/PS1 Mice with Poorly Controlled Diabetes Mellitus. Journal: Molecular Neurobiology. Year, volume, first and last pages: 2015; 53(4):2685-97. Impact factor: 5.39. Quartile/Decile in the year of publication: First quartile (Neurosciences).
3. Authors: Infante-Garcia C, Ramos-Rodriguez JJ, Garcia-Alloza M. Title: Prediabetes and type 2 diabetes implication in central proliferation and neurogenesis. Journal: Neural Regen Res. Year, volume, first and last pages: 2015 Jan;10(1):28-9. Impact factor: 0.96. Quartile/Decile in the year of publication: Fourth quartile (Neurosciences).
4. Authors: García-Doncel L, Triviño Ibáñez EM, Sánchez García I, Baena Nieto G. Title: Growth hormone deficiency secondary to pituitary iron deposition in a pyruvate kinase deficient patient]. Journal: Int J Endocrinol. Med Clin (Barc). Year, volume, first and last pages: 2015 Jun 22;144(12):573-4. Impact factor: 2.37. Quartile/Decile in the year of publication: Third quartile (Endocrinology and Metabolism).
5. Authors: Diaz-Ganete A, Baena-Nieto G, Lomas-Romero IM, Lopez-Acosta JF, Cozar-Castellano I, Medina F, Segundo C, Lechuga-Sancho AM. Title: Ghrelin's Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality. Journal Int J Endocrinol. Year, volume, first and last pages: 2015;2015:235727. Impact factor: 2.37. Quartile/Decile in the year of publication: Third quartile (Endocrinology and Metabolism).
6. Authors: Chacón PJ, del Marco Á, Arévalo Á, Domínguez-Giménez P, García-Segura LM, Rodríguez-Tébar A. Title: Cerebellin 4, a synaptic protein, enhances inhibitory activity and resistance of neurons to amyloid-β toxicity. Journal Neurobiol Aging. Year, volume, first and last pages: 2015. Feb;36(2):1057-71. Impact factor: 5.15. Quartile/Decile in the year of publication: First decile (Geriatrics).

1. Authors: Ramos-Rodriguez JJ, Ortiz-Barajas O, Gamero-Carrasco C, Romero de la Rosa P, Infante-Garcia C, Zopeque-Garcia N, Lechuga-Sancho AM, Garcia-Alloza M. Title: Prediabetes-induced vascular alterations exacerbate central pathology in APPswe/PS1dE9 mice. Journal: Psychoneuroendocrinology. Year, volume, first and last pages: 2014, 48:123-35. Impact factor: 4.94. Quartile/Decile in the year of publication: First quartile (Psychiatry).
2. Authors: Benavente-Fernández I, Lubian-Lopez SP, Jiménez-Gomez G, Lechuga-Sancho AM, Garcia-Alloza M Title: Low-voltage pattern and absence of sleep-wake cycles are associated with severe hemorrhage and death in very preterm infants. Journal: Eur J Pediatr. Year, volume, first and last pages: 2014; 174(1):85-90. Impact factor: 1.89. Quartile/Decile in the year of publication: Second quartile (Pediatrics).
3. Authors: Ramos-Rodriguez JJ, Molina-Gil S, Ortiz-Barajas O, Jimenez-Palomares M, Perdomo G, Cozar-Castellano I, Lechuga-Sancho AM, Garcia-Alloza M. Title: Central proliferation and neurogenesis is impaired in type 2 diabetes and prediabetes animal models. Journal: Plos one. Year, volume, first and last pages: 2014; Feb 20;9(2):e89229. Impact factor: 3.7. Quartile/Decile in the year of publication: First quartile (Multidisciplinary sciences).

• NETWORK NAME: HEAT network Harvard Exchange Alumni Training Programm. Internacional. PRINCIPAL INVESTIGATOR: Martin Ingelson (Universidad de Upsala, Upsala, Suecia) and Alberto Lleó (Hospital Sta Cruz y San Pablo, Barcelona). COLLABORATOR: Christine von Arnim (University of Göttingen), Lars Bertram (University of Ulm), Karin Danzer, Dra. Annakaisa Haapasalo (University of Kuopio), Mikko Hiltunen (University of Eastern Finland), Martin Ingelsson (University of Uppsala), Jochen Klucken (University of Erlangen), Dra. Christina Lill (University of Lübeck), Tiago Outeiro (University of Göttingen), Tara Spires-Jones (University of Edinburg), Monica García-Alloza (Universidad de Cadiz-INIBICA).