TDP‐43 Neuronal Cytoplasmic Inclusions in the Amygdala of Patients with Advanced Alzheimer Disease

Abstract

TAR DNA binding protein‐43 (TDP‐43)‐immunoreactive neuronal cytoplasmic inclusions (NCIs), characteristically associated with frontotemporal lobar degenerations (FTLD‐U and FTLD‐MND), have been found in the hippocampal dentate granule cells of about 20% of cases with advanced Alzheimer disease (AD). The extent and distribution of TDP‐43 pathology in brain regions other than hippocampus in AD is not known, especially in AD cases without hippocampal NCIs.Sections of hippocampus, amygdala, neocortex, and medulla from patients with clinical dementia and pathologic features of AD were analyzed for the presence of TDP‐43‐immunoreactive NCIs.22 cases of advanced AD (Braak Stage V‐VI) without hippocampal NCIs and 23 cases of advanced AD with hippocampal NCIs were included. 6 hippocampal‐negative cases (27%) had TDP‐43 positive NCIs in the amygdala. All 23 cases of hippocampal‐positive cases had numerous TDP‐43 NCIs in the amygdala, with decreasing density of NCIs in the other brain regions.In summary, TDP‐43 immunoreactive NCIs are found predominantly in the medial temporal structures in advanced AD, and the amygdala appears to be the area most vulnerable.