P1‐189: Community‐based Comprehensive Neuropathological Survey in the Elderly Reveals Wider Range of Neurodegenerative Pathologies Than Assumed

Neuropathological studies on elderly individuals emphasize the importance of mixed pathologies focusing on Alzheimer's disease (AD), cerebrovascular pathology, and presence of Lewy bodies. There is a relative paucity of data on less frequent neurodegenerative disease forms. We examined individuals in the frame of a longitudinal community-based study (VITA) living in a restricted area of Vienna. Formalin fixed, paraffin-embedded tissue blocks of different neocortical and subcortical regions, hippocampus, brainstem and cerebellum were processed for neuropathological evaluation. This included systematic anatomical mapping of deposits of neurodegeneration-related proteins (amyloid-beta, tau, pTDP-43, alpha-synuclein) and classification according to recent diagnostic criteria. Brains of 200 patients (age 77-86) were evaluated. In the total cohort (i.e. clinically examined and demented, and clinically not examined individuals) approximately one-third of examined brains showed 1) alpha-synucleinopathy mainly in the form of Lewy body disease, including amygdala-predominant form, but also as multiple system atrophy; 2) TDP-43 proteinopathy mainly restricted to the limbic regions as concomitant pathology, however, also FTLD-TDP as primary pathology; or 3) tauopathy, including progressive supranuclear palsy, argyrophilic grain disease, and tauopathy with peculiar astrogliopathy [1]. Complex combinations of these proteinopathies with less obvious AD changes were also noted. Our comprehensive approach revealed that non-AD degenerative diseases, including atypical phenotypes of tauopathy, complex constellations, or disorders thought to present in earlier age (i.e. FTLD-TDP), are more frequent than assumed. Combination of these neurodegenerative pathologies may lower the threshold for symptomatic cognitive decline even with minor AD-related change or cerebrovascular disease. Our observations 1) support the concept of differentiated therapeutical approaches for dementia and 2) have implications for biomarker research by proposing a comprehensive evaluation of distinct neurodegeneration-related proteins in body fluids. References: 1: Kovacs GG, et al. A peculiar constellation of tau pathology defines a subset of dementia in the elderly. Acta Neuropathol. 2011;122:205-22. 2: Kovacs GG, et al. Protein coding of neurodegenerative dementias: the neuropathological basis of biomarker diagnostics. Acta Neuropathol. 2010;119:389-408.