Observation on pathological TDP ⁃ 43 in amygdala of patients with common neurodegenerative diseases

Objective To observe the detection rate, morphological characteristics and deposition degree of pathological trans⁃activation response DNA binding protein 43 (TDP⁃43) in several common neurodegenerative diseases, and to explore its pathological significance. Methods A total of 15 cases with a history of hospitalization in the Second Medical Center, Chinese PLA General Hospital from January 1994 to September 2019 were retrospectively collected, including 5 cases of Alzheimer's disease (AD), 3 cases of Parkinson's disease (PD), 2 cases of progressive supranuclear palsy (PSP), and 5 cases of normal aging brain. HE staining, Lucas fast blue (LFB) staining, Gallyas⁃Braak silver staining, and immunohistochemical staining of β⁃amyloid (Aβ), AT8, phosphorylated TDP⁃43 and α⁃synuclein (α⁃Syn) were performed for amygdala tissue sections. The pathological morphological characteristics of pathological TDP⁃43 protein was observed under a light microscope, and the pathological TDP⁃43 protein was graded by semi⁃quantitative method. Results Phosphorylated TDP⁃43 antibody staining was found in 5/15 of aging brain amygdala tissue, including 2 cases of AD, one case of PD, and 2 cases of normal aging brain. Among them, severe pathological TDP⁃43 protein deposition and mild short neurodystrophy filaments were found in the amygdala of 2/5 cases of AD, mainly neuronal cytoplasmic inclusion bodies. Cytoplasmic inclusions and short neurodystrophy filaments in rare neurons of amygdala in 1/3 cases of PD. Rare or mild neuronal cytoplasmic inclusions and rare short neurodystrophy filaments were found in the amygdala of 2/5 normal aging brain. Two cases of PSP showed negative staining for phosphorylated TDP⁃43 antibody in amygdala. No long amygdala neurodystrophy filaments were found in the 15 patients. No glial cytoplasmic inclusions and neuronal intranuclear inclusions were found in PD, PSP and normal aging brain. Conclusions Pathological TDP⁃43 protein is most severe in the amygdala of AD and may accelerate cognitive decline in AD or lower the threshold of cognitive dysfunction.