Clinicopathological features of primary tauopathies: a brain bank series

This study presents the first comprehensive clinicopathological analysis of primary tauopathies from the Neurological Foundation Human Brain Bank (NFHuBB). Primary tauopathies are a heterogeneous group of neurodegenerative disorders, defined by abnormal tau protein deposition as the core pathological feature. They are further defined by the absence of an additional pathological driver. Historically, they were often accepted into brain banks as Alzheimer's, Parkinson's, or dementia cases.

Here, we retrospectively examined all brain donations to the NFHuBB from 1994 to 2022 to identify cases of primary tauopathy, excluding those with known secondary causes such as repetitive head trauma. This is a national-level, single brain bank series. Detailed clinical records, demographic data, and post-mortem pathological investigations, including immunohistochemistry, were analysed to establish clinical and pathological diagnoses according to current criteria.

Fifteen cases were identified, spanning argyrophilic grain disease, primary age-related tauopathy, corticobasal degeneration, genetic frontotemporal dementia, and progressive supranuclear palsy. The mean age of onset was 69 years, with average survival of 6 years. Notably, only 47% of cases showed concordance between clinical and pathological diagnosis, underscoring diagnostic challenges. Neuropathological review revealed marked diversity in tau pathology and regional vulnerability, with most cases demonstrating both neuronal and glial tau pathology.

This case series highlights the complexity and heterogeneity of primary tauopathies and the critical role of post-mortem neuropathological examination for diagnosis. By making fixed and frozen tissue, and clinical data available for national and international dissemination, this study provides a valuable resource to advance global research into the pathogenesis and classification of tauopathies. Furthermore, this work highlights the important role of brain banking in the study of rare diseases.