Fatty Aspirin: A New Perspective in the Prevention of Dementia of Alzheimers Type?

Abstract

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.

Neuroprotective and Ameliorative Actions of Polyunsaturated Fatty Acids Against Neuronal Diseases: Beneficial Effect of Docosahexaenoic Acid on Cognitive Decline in Alzheimer’s Disease

“…Thus, DHA-based neuroprotection may involve anti-inflammatory processes that reduce AA availability. Although contradictory data have been published in epidemiological and clinical studies regarding nonsteroidal anti-inflammatory drugs in the prevention and treatment of AD, DHA together with aspirin has been proposed as a strategy to explore its potential for preventing neurodegenerative diseases such as AD (86). Further knowledge of the molecular mechanisms through which increases in the levels of NPD1 and other metabolites of DHA enhance neuronal health is required to understand how decreased levels of these important metabolites might contribute to the pathogenesis of AD and other degenerative diseases.…”

Cu/Zn superoxide dismutase (SOD1) induction is implicated in the antioxidative and antiviral activity of acetylsalicylic acid in HCV-expressing cells

“…Aspirin (acetylsalicylic acid, ASA), a nonsteroidal antiinflammatory drug, is now widely used for the prevention of cardiovascular disease (4,16) for reducing the risk of Alzheimer's disease (19,33), and for colon cancers (3,36). Because its mechanism consists in inhibiting cyclooxygenase activity, most studies have focused on studying this mechanism of action.…”

Metabolic Syndrome and Neurotrophins: Effects of Metformin and Non-Steroidal Antiinflammatory Drug Treatment

“…Recently, large meta-analyses have examined the increased risk of cardiovascular events in people with MS [18][19][20][21][22]. These studies showed that MS was associated with a 2-fold increase in cardiovascular outcomes and a 1.5-fold increase in all-cause mortality rates while the cardiovascular risk remained high in patients with MS but without DM.…”

“…No data are available about either the action of Mf or the influence of non-steroidal antiinflammatory drugs (NSAIDs) on circulating levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) [19,20].…”