Longitudinal Assessment of a Transgenic Animal Model of Tauopathy by FDG-PET Imaging

Issue title: Propagation of Tau Pathology

Guest editors: Miguel Medina and Jesús Avila

Article type: Research Article

Authors: de Cristóbal, Javier^{a; b; *} | García-García, Luis^{a; c} | Delgado, Mercedes^a | Pérez, Mar^d | Pozo, Miguel A.^{a; e} | Medina, Miguel^{b; 1}

Affiliations: [a] CAI de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII 1, Madrid, Spain | [b] Noscira SA, Tres Cantos (Madrid), Spain | [c] Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Pza. Ramón y Cajal s/n, Madrid, Spain | [d] Departamento de Anatomía Histología y Neurociencia, Facultad de Medicina UAM, Madrid, Spain | [e] Instituto Tecnológico PET, c/Manuel Bartolomé Cossío, Madrid, Spain

Correspondence: [*] Correspondence to: Javier de Cristóbal, CAI de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII 1, 28040 Madrid, Spain. E-mail: [email protected].

Note: [1] Present address: CIBERNED (Centro de Investigación en Red sobre Enfermedades Neurodegenerativas), Madrid, Spain.

Abstract: Abnormal levels and hyperphosphorylation of tau protein have been proposed as the underlying cause of a group of neurodegenerative disorders collectively known as ‘tauopathies’. The detrimental consequence is the loss of affinity between this protein and the microtubules, increased production of fibrillary aggregates, and the accumulation of insoluble intracellular neurofibrillary tangles. A similar phenotype can be observed in various preclinical models, which have been generated to study the role of tau protein in neurodegenerative disorders. In this study, we have analyzed the brain metabolic activity in an animal model of tauopathy (tauVLW transgenic mice), which has been previously reported to mimic some of the phenotypic features of these disorders. By using a non-invasive technique, positron emission tomography (PET), a longitudinal non-clinical follow up study was carried out during most of the lifespan of these transgenic mice, from the youth to the senescence stages. The results obtained point out to an aging-dependent decrease in 18F-fluoro-deoxyglucose (FDG) uptake in the cerebral areas analyzed, which was already significant at the adult age, i.e., 11 months, and became much more prominent in the oldest animals (19 months old). This observation correlates well with the histopathological observation of neurodegeneration in brain areas where there is overexpression of tau protein.

Keywords: Brain metabolism, longitudinal, neuroimaging, tau protein, transgenic mouse

DOI: 10.3233/JAD-132276

Journal: Journal of Alzheimer's Disease, vol. 40, no. s1, pp. S79-S89, 2014