Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the abnormal accumulationof amyloid-b (Ab) plaques and Tau neurofibrillary tangles (NFTs) in the brain, giving rise to widespreadsynaptic loss, inflammation, oxidative damage and neuronal death. Some of these processes begindecades before the onset of clinical symptoms, constituting a unique opportunity for the earlydiagnosis of the disease and eventual evaluation of the response to treatment. However, to date, thereis no effective treatment for AD available in the market nor is there any reliable option for the earlyassessment of the disease. The diagnosis is therefore mainly based on clinical symptoms, which occurat later stages of the disease, when it is much too late for successful medical intervention. Toovercome this growing problem and provide AD patients with better treatment options, there is anurgent need to identify new disease biomarkers to (i) enable longitudinal and non-invasive monitoringof disease progression, (ii) enable a targeted approach for new treatment, diagnostic and theragnosticstrategies and (iii) provide with new tools for treatment response evaluation.
Alzheimer’s pathophysiology can be investigated non-invasively by the means of positron emissiontomography (PET) imaging, using specifically designed radiotracers to detect biological hallmarks of thedisease in vivo. At the same time, even though animal models of AD lack on recapitulating thecomplete spectra of the disease, they offer a true understanding of the underlying mechanisms of thedisease and have proven to be invaluable in the preclinical evaluation of potential therapeuticinterventions and diagnostic tools. In this sense, the Tg-F344 AD rat model manifests age-dependentcerebral amyloidosis that precedes tauopathy, gliosis, apoptotic loss of neurons in the cerebral cortexand hippocampus, and cognitive disturbance. Overall, the model constitutes a step forward for thestudy of the disease pathophysiology compared to previously used transgenic mice models.
In this study, we looked into the longitudinal progression of some of the pathophysiological aspects ofAD (e.g. Tau deposition, amyloid plaques, neuroinflammation, enzymatic levels and synaptic density) inthe Tg-F344 rat model of AD, by acquiring PET images at different time points with an array of selectedradiotracers. At the same time, we monitored age-matched wild type (WT) littermates under the sameconditions for baseline purposes. We supported our findings with ex vivo imaging techniques (e.g.autoradiography and immunofluorescence) from harvested brain tissue and assessed the cognitivestatus of the animals under different behavior tests. Overall, we examined the ability of PETradiotracers to monitor disease progression overtime, while we gained a better understanding on thecharacterization of this model for future studies. Further steps in this project will include the use of thisrat model for treatment response evaluation of potential disease modifying drug candidates.