Title:Alzheimer’s Disease Genetic Risk Factor APOE-ε4 Also Affects Normal Brain Function
Volume: 13
Issue: 11
Author(s): Amanda M. Di Battista, Nicolette M. Heinsinger, G. William Rebeck
Affiliation:
关键词:
载脂蛋白E、淀粉、内嗅皮层、树突棘、海马体、目标替代老鼠、预防、风险因素。
摘要: APOE-ε4 is the strongest genetic risk factor for Alzheimer’s disease (AD), and is associated
with an increase in the levels of amyloid deposition and an early age of onset. Recent data demonstrate
that AD pathological changes occur decades before clinical symptoms, raising questions
about the precise onset of the disease. Now a convergence of approaches in mice and humans has
demonstrated that APOE-ε4 affects normal brain function even very early in life in the absence of
gross AD pathological changes. Normal mice expressing APOE4 have task-specific spatial learning
deficits, as well as reduced NMDAR-dependent signaling and structural changes to presynaptic and
postsynaptic compartments in neurons, particularly in hippocampal regions. Young humans possessing
APOE-ε4 are more adept than APOE-ε4 negative individuals at some behavioral tasks, and functional
magnetic resonance imaging has shown that inheritance of APOE-ε4 has specific effects on
medial temporal brain activities. These findings suggest that inheritance of APOE-ε4 causes life long
changes to the brain that may be related to the late risk of AD. Several possible mechanisms of how
APOE-ε4 could affect brain neurochemistry, structure, and function are reviewed.