Defining an MRI signature of tau pathology

Alzheimer's disease (AD) is the most common form of dementia. Most scientists agree that early detection and prevention would be more effective than trying to cure the disease. However, current AD biomarkers as lumbar puncture or PET are too invasive, too expensive, and not widely available. The most currently used biomarker for AD in memory clinics is hippocampal atrophy assessed by MRI. Yet, this measure is not specific for AD and is common to other diseases. We therefore aim to develop more specific MRI biomarkers for AD. The aim of this research project is to study the impact of AD neuropathologies, on the anatomy, specifically in the medial temporal lobe (MTL) which is affected in many age-related neurodegenerative diseases. Ultimately, we aim to refine AD MRI biomarkers to make them more specific for AD neuropathologies: amyloid and tau. Because tau was shown to be more correlated to atrophy than amyloid, we will most focus on tau pathology.To this end, we will use a double original approach by studying on one hand the impact of tau on MTL atrophy using in-vivo PET and MRI data; and on the other hand, we will identify AD specific lesions with the finest spatial resolution using ultra-high field MRI on post-mortem brain samples. First, we will evaluate the in-vivo association between the anatomy and tau pathology by correlating in-vivo measurements of tau pathology quantified by Tau-PET with a second-generation tracer (18F-MK6240) with measures of hippocampal atrophy and cortical thinning assessed by 3T MRI in a large cohort of patients diagnosed with AD and controls. Subsequently, we will use ultra-high field MRI (11.7T) and detailed histopathological analysis on post-mortem brains of AD patients and controls to identify and describe atrophy due to AD-specific neuropathologies (amyloid and tau pathology) with extremely fine spatial resolution. Finally, to further refine the current AD-biomarkers, we aim to replicate our observations from post-mortem analysis at lower MRI fields, available in living humans. To this end, we will perform MRI scans of the same MTL specimens at 3T and 7T and propose 7T MRI to a small subset of living patients before finally exporting the results to 3T, a field commonly available in the clinic.