A defining pathological feature of many neurodegenerative diseases is the assembly of proteins into disease-specific amyloid structures. Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative pathology associated with repetitive head trauma and exposure to blast waves and is characterised by a distinct anatomical pattern of hyperphosphorylated-tau (p-tau) deposition at the depths of cortical sulci. P-tau aggregates are also implicated in over 20 other neurodegenerative diseases, including Alzheimer’s Disease (AD) and Pick’s Disease (PiD), however the ultrastructure of tau in CTE is unique. The lack of in vitro methods for recombinant production and characterisation of pathological amyloids has hampered progress towards improved neurodegeneration detection and management during life and is particularly apparent for CTE which can only be definitively diagnosed by postmortem examination of affected brains. Additionally, clinical methods for accurate and rapid identification of amyloid polymorphs in patients do not exist. Development of high-specificity small molecule binders for disease-associated tau polymorphs would mitigate these shortcomings and may provide a tool compatible with patient screening during life. This work reports on an in vitro system for recombinantly producing tau amyloid fibrils comprising both CTE and AD specific filament conformations. Fibrils produced were screened against a suite of fluorescent amyloid-binding probes and the excitation/emission spectral information utilised to identify unique spectral maps for disease-specific conformations of tau. Full in vitro spectral information will be compared and validated with ex vivo fibrils ascertained from CTE and AD patients within serial sections from human cortex. We predict that these investigations will result in the ability to biochemically discern tau-polymorphs such as those implicated in CTE and AD, and ultimately will guide research towards improved diagnosis and management of CTE premortem.