Longitudinal tau accumulation in non-amnestic phenotypes of Alzheimer’s disease

• Applicant: Ganna Blazhenets, Ph.D.
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2021 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 493328842

Alzheimer’s disease (AD) is a degenerative brain disorder characterized by the presence of amyloid-β and tau tangles pathologies. The prevalence of AD increases with age and has a tremendous socio-economic impact on families and health systems. The clinical representation of AD is heterogeneous and expands beyond the traditionally described older-age amnestic-predominant syndrome with pronounced memory deficits. Atypical non-amnestic phenotypes represent one-third of patients with young-onset AD and are more likely to be misdiagnosed or to receive a delayed diagnosis, as their symptoms might be attributed to other neurodegenerative diseases, life stresses or psychiatric illness. Flortaucipir (FTP) is a radiotracer of positron emission tomography (PET) that binds to paired helical filaments of tau and can be used to visualize and quantify tau pathology in the brain. Given that the different phenotypes have diverse spatial distribution of tau pathology at baseline, it is likely that they will follow distinct pathways and show tau burdens in different areas over time. Longitudinal tau PET assessments are essential for testing whether a patient’s specific factors as age, sex, cognitive functioning, genotype, etc. and their interplay are associated with more aggressive biological processes (e.g., higher rates of tau accumulation and other pathways of spatial spread) than in typical AD. To this end, the proposed project aims to explore the differences in the distribution of tau accumulation in patients with non-amnestic and amnestic phenotypes of AD, identify interactions between regions with increased tau accumulation, and explore whether the spread of tau pathology in different phenotypes may be predicted based on baseline pattern and connections between the most affected regions. The identification of longitudinal tau patterns may be employed as a tool of precision medicine in AD to better characterize disease heterogeneity, ensure optimal monitoring of individual disease progression, treatment, as well as prognosis, and patient counseling.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Renaud La Joie, Ph.D.