Comment: Telomeres in AD - The long and the short of it

摘要

DNA damage and telomere shortening are fundamental aging-related processes that have been explored as a mechanism for Alzheimer disease (AD) pathogenesis. This seems rational given that advanced age is the greatest risk factor for late-onset sporadic AD. Despite the attractiveness of the "telomere hypothesis" of AD, work in this area has been inconclusive, with studies reporting often contradictory results. While peripheral lymphocytes and other mitotically active tissues may exhibit telomere shortening in AD vs controls without dementia, hippocampal and cerebellar tissues show no such association. This may not be surprising, because neurons have extremely limited mitotic activity; therefore, DNA replication, essential for telomere shortening, is a rare event. Recent animal work has further complicated the field, demonstrating that telomere shortening actually improved spatial learning and reduced amyloid deposition as well as microglial activation in amyloid-producing APP23 transgenic mice.