Pomponi M, Di Gioia A, Bria P, Pomponi M F L
Catholic University of Sacred Heart (UCSC), Psychiatric Department, Rome, Italy.
Curr Alzheimer Res. 2008 Oct;5(5):422-31. doi: 10.2174/156720508785908892.
Alzheimer's disease (AD) leads to a dramatic decline in cognitive abilities and memory. A more modest disruption of memory often occurs in normal aging and the same circuits that are devastated through degeneration in AD are vulnerable to sub-lethal age-related changes that alter synaptic transmission. There are numerous indications that aberrant plasticity is critically involved in Alzheimer's. Is ageing itself the major risk factor for AD? Is AD an acceleration of normal ageing? We assume that the ability of the brain is to modify its own structural organization and functioning which is liable to become impaired in ageing until it becomes dramatically impaired in Alzheimer's. Moreover, ageing can compromise the conversion of dietary alpha-linolenic acid (ALA) to docosahexaenoic acid (DHA). DHA regulates synaptogenesis and affects the synaptic structure, and synapse density is reduced in ageing. DHA and newly identified DHA-derived messenger, neuroprotecting D1 (NPD1), protect synapses and decrease the number of activated microglia in the hippocampal system. Delaying AD onset by a few years would reduce the number of the cases of dementia in the community. DHA (and NPD1?) and aspirin induce brain-derived neurotrophic factor (BDNF) protein expression and this protein has a crucial role in neuronal survival. The authors--in view of the increased neuroinflammatory reaction frequently observed during normal brain ageing--suggest the long-term use of "fatty aspirin", an association of DHA and/or NPD1 and aspirin (or nitroaspirin), to postpone, or prevent, the structural neurodegeneration of the brain.
阿尔茨海默病（AD）会导致认知能力和记忆力急剧下降。在正常衰老过程中，记忆力通常会出现较为轻微的受损，而在AD中因神经退行性变而遭到破坏的相同神经回路，也容易受到与年龄相关的亚致死性变化的影响，这些变化会改变突触传递。有大量迹象表明，异常可塑性在阿尔茨海默病中起着关键作用。衰老本身是AD的主要危险因素吗？AD是正常衰老的加速过程吗？我们认为，大脑具有改变自身结构组织和功能的能力，而这种能力在衰老过程中容易受损，直至在阿尔茨海默病中严重受损。此外，衰老会影响膳食中的α-亚麻酸（ALA）向二十二碳六烯酸（DHA）的转化。DHA调节突触形成并影响突触结构，且衰老过程中突触密度会降低。DHA以及新发现的源自DHA的信使分子——神经保护因子D1（NPD1），可保护突触并减少海马系统中活化小胶质细胞的数量。将AD发病推迟数年将减少社区中痴呆症病例的数量。DHA（以及NPD1？）和阿司匹林可诱导脑源性神经营养因子（BDNF）蛋白表达，而这种蛋白在神经元存活中起着关键作用。鉴于在正常脑衰老过程中经常观察到神经炎症反应增加，作者建议长期使用“脂肪阿司匹林”，即DHA和/或NPD1与阿司匹林（或硝基阿司匹林）的组合，以延缓或预防大脑的结构性神经退行性变。
