Brains of rhesus monkeys display A? deposits and glial pathology while lacking A? dimers and other Alzheimer's pathologies.

ABSTRACT: Cerebral amyloid beta (A?) deposits are the main early pathology of Alzheimer's disease (AD). However, abundant A? deposits also occur spontaneously in the brains of many healthy people who are free of AD with advancing aging. A crucial unanswered question in AD prevention is why AD does not develop in some elderly people, despite the presence of A? deposits. The answer may lie in the composition of A? oligomer isoforms in the A? deposits of healthy brains, which are different from AD brains. However, which A? oligomer triggers the transformation from aging to AD pathogenesis is still under debate. Some researchers insist that the A? 12-mer causes AD pathology, while others suggest that the A? dimer is the crucial molecule in AD pathology. Aged rhesus monkeys spontaneously develop A? deposits in the brain with striking similarities to those of aged humans. Thus, rhesus monkeys are an ideal natural model to study the composition of A? oligomer isoforms and their downstream effects on AD pathology. In this study, we found that A? deposits in aged monkey brains included 3-mer, 5-mer, 9-mer, 10-mer, and 12-mer oligomers, but not 2-mer oligomers. The A? deposits, which were devoid of A? dimers, induced glial pathology (microgliosis, abnormal microglia morphology, and astrocytosis), but not the subsequent downstream pathologies of AD, including Tau pathology, neurodegeneration, and synapse loss. Our results indicate that the A? dimer plays an important role in AD pathogenesis. Thus, targeting the A? dimer is a promising strategy for preventing AD.

SUBMITTER: Zhang J 

PROVIDER: S-EPMC6612634 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature