Increased expression of the proapoptotic presenilin associated protein is involved in neuronal tangle formation in human brain

作者：Chen Yang, Zhongping Sun, Juan Jiang, Xiao-Lu Cai, Yan Wang, Hui Wang, Chong Che, Ewen Tu, Aihua Pan, Yan Zhang, Xiaoping Wang, Mei‐Zhen Cui, Xuemin Xu, Xiao‐Xin Yan, Qi‐Lei Zhang · 发表于：Scientific Reports · 年份：2024 · DOI：10.1038/s41598-024-77026-0 · 被引用次数：7 · 研究领域：Alzheimer's disease research and treatments、Neuroscience and Neuropharmacology Research、Glycosylation and Glycoproteins Research

Presenilin-associated protein (PSAP) is a mitochondrial proapoptotic protein as established in cell biology studies. It remains unknown whether it involves in neurodegenerative diseases. Here, we explored PASP expression in adult and aged human brains and its alteration relative to Alzheimer-disease (AD)-type neuropathology. In pathology-free brains, light PASP immunoreactivity (IR) occurred among largely principal neurons in the cerebrum and subcortical structures. In the brains with AD pathology, enhanced PSAP IR occurred in neuronal and neuritic profiles with a tangle-like appearance, with PSAP and pTau protein levels elevated in neocortical lysates relative to control. Neuronal/neuritic profiles with enhanced PSAP IR partially colocalized with pTau, but invariably with Amylo-Glo labelled tangles. The neuronal somata with enhanced PASP IR also showed diminished IR for casein kinase 1 delta (Ck1δ), a marker of granulovacuolar degeneration; and diminished IR for sortilin, which is normally expressed in membrane and intracellular protein sorting/trafficking organelles. In old 3xTg-AD mice with β-amyloid and pTau pathologies developed in the brain, PSAP IR in the cerebral sections exhibited no difference relative to wildtype mice. These findings indicate that PSAP upregulation is involved in the course of tangle formation especially in the human brain during aging and in AD pathogenesis.