Vallino Costassa Elena, Fiorini Michele, Zanusso Gianluigi, Peletto Simone, Acutis Pierluigi, Baioni Elisa, Maurella Cristiana, Tagliavini Fabrizio, Catania Marcella, Gallo Marina, Faro Monica Lo, Chieppa Maria Novella, Meloni Daniela, D'Angelo Antonio, Paciello Orlando, Ghidoni Roberta, Tonoli Elisa, Casalone Cristina, Corona Cristiano
Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Torino, Italy.
Dipartimento di Scienze Neurologiche Biomediche e del Movimento, Universitá di Verona, Policlinico "G.B. Rossi" Borgo Roma, Verona, Italy.
J Alzheimers Dis. 2016;51(3):875-87. doi: 10.3233/JAD-151007.
Amyloid-β (Aβ) deposits are seen in aged individuals of many mammalian species that possess the same aminoacid sequence as humans. This study describes Aβ deposition in 102 clinically characterized cattle brains from animals aged 0 to 20 years. Extracellular and intracellular Aβ deposition was detected with 4G8 antibody in the cortex, hippocampus, and cerebellum. X-34 staining failed to stain Aβ deposits, indicating the non β-pleated nature of these deposits. Western blot analysis and surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry revealed in Tris, Triton, and formic acid fractions the presence of different Aβ peptides, characterized mainly by C-terminally truncated forms. Exploration of the genetic variability of APOE, PSEN1, and PSEN2 genes involved in Alzheimer's disease pathogenesis revealed several previously unreported polymorphisms. This study demonstrates certain similarities between Aβ deposition patterns exhibited in cattle brains and those in the human brain in early stages of aging. Furthermore, the identification of the same Aβ peptides reported in humans, but unable to form aggregates, supports the hypothesis that cattle may be protected against amyloid plaque formation.
在许多与人类具有相同氨基酸序列的哺乳动物物种的老年个体中都可见淀粉样β蛋白(Aβ)沉积。本研究描述了102头年龄在0至20岁之间、具有临床特征的牛脑内的Aβ沉积情况。使用4G8抗体在大脑皮层、海马体和小脑中检测到了细胞外和细胞内的Aβ沉积。X - 34染色未能对Aβ沉积物进行染色,这表明这些沉积物不具有β折叠结构。蛋白质印迹分析和表面增强激光解吸/电离飞行时间(SELDI - TOF)质谱分析显示,在Tris、Triton和甲酸组分中存在不同的Aβ肽,其主要特征为C端截短形式。对参与阿尔茨海默病发病机制的APOE、PSEN1和PSEN2基因的遗传变异性进行探索,发现了一些此前未报道的多态性。本研究表明,牛脑内Aβ沉积模式与人类大脑衰老早期的沉积模式存在某些相似之处。此外,在牛脑中鉴定出了与人类相同但无法形成聚集体的Aβ肽,这支持了牛可能对淀粉样斑块形成具有抵抗力的假说。