动物造模,阿兹海默病 z-bio 2022-09-30 516

　　Inoculation of mice with brain homogenates from sporadic Alzheimer's disease patients elicited cerebral amyloid deposition in recipients, suggesting that the amyloid beta (Aβ) peptide may self-proliferate as a prion.

　　Stanley Prusiner and colleagues tested whether inoculating the brain with two synthetic amyloid beta (Aβ) peptides -- consisting of 40 or 42 amino acids, respectively, aggregated into amyloid fibrils -- might be engineered to express Plaque-forming reporter mice induced plaques that are hallmarks of Alzheimer's disease. The authors report that this synthetic preparation of amyloid beta (Aβ) peptide 40, which consists of long, narrow fibrils, produces both peptides in the corpus callosum, hippocampus, and cerebral cortex of recipient mice. plaques, whereas preparations of amyloid beta (Aβ) peptide 42 composed of short fibrils elicited smaller, more numerous plaques, mainly containing amyloid beta (Aβ) peptide 42 . However, treatment of these amyloid preparations with a low concentration of detergent SDS prior to inoculation eliminated the observed differences in plaque content, abundance and distribution. The authors propose that the type of amyloid beta (Aβ), which may contribute to the pathological heterogeneity seen in Alzheimer's patients, may help to stratify treatment for patients.

　　In a related study, Prusiner and colleagues tested whether different aggregates of amyloid beta (Aβ) spread throughout the brains of different Alzheimer's patients, potentially complicating drug development. When the authors inoculated transgenic mice with brain homogenates from two different genetic forms of Alzheimer's disease -- either carrying an arctic mutation that altered the sequence of these amyloid beta (Aβ) peptides, Or carry a Swedish mutation that appears outside of these sequences—different patterns and abundances of brain amyloid deposits emerge. Furthermore, these differences persisted when these amyloid beta (Aβ) types were continuously proliferated in mice, suggesting prion-like transmissibility of these types. Monoclonal antibodies developed against a specific type of amyloid beta (Aβ) for passive Alzheimer's immunotherapy may not be effective against other types, according to the authors, shedding light on a series of past failures of such approaches. A plausible partial explanation.