Historically, clinicians have recognized patients with neurodegenerative dementias based on their clinical symptoms. In recent years, basic science advances have allowed researchers to re-categorize these diseases based on molecular phenotype, i.e. which toxic, misfolded disease protein aggregates are observed in the brain post-mortem, such as beta amyloid (Aβ) and hyperphosphorylated tau (HP-tau) in Alzheimer's Disease (AD); tau, TAR DNA-binding protein of 43 kDa (TDP-43), or fused in sarcoma (FUS) in frontotemporal dementia (FTD), and alpha-synuclein in Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB).1 These pathological changes are considered early events in a cascade that begins at the synaptic and neuronal levels and ultimately leads to the clinical syndrome. Within this temporal window, quantifiable biological, imaging, and physiological markers of pathology have been identified that can be considered in vivo intermediate phenotypes. Such surrogate markers of pathology can clarify disease pathophysiology, i.e. link the molecular phenotype to clinical symptoms and have the potential to facilitate earlier, more accurate diagnosis and monitoring of disease progression. In AD, PET amyloid ligands enable in vivo mapping of cerebral Aβ deposition,2 whereas structural
