Issue link: https://cp.revolio.com/i/602310
Page 28 | Abby's Magazine - www.AbbysMag.com Alzheimer's disease and mitochondrial dysfunction is the finding that ApoE4, a genetic variant associated with Alzheimer's disease and amyloid beta deposition within the brain, seems to play a role in disrupting mitochondrial respiratory chain function. Dysfunctional mitochondria are important mediators of amyloid beta toxicity. Mitochondrial dysfunction contributes to an increased burden of oxidative stress as well, which itself is another mediator of amyloid beta toxicity. Mitochondrial dysfunction and oxidative stress then drive the formation of additional amyloid beta, creating a vicious, self-propagating cycle that ultimately leads to neuron death. Excitotoxicity Glutamate is the most abundant excitatory neurotransmitter in the brain and is necessary for normal brain function. However, too much glutamatergic neurotransmission can be toxic to neurons, a phenomenon known as "excitotoxicity". Excitotoxicity is thought to contribute to neuronal degeneration in Alzheimer's disease because it is promoted by amyloid beta, neurofibrillary tangles, mitochondrial dysfunction, and oxidative stress among other factors. Glutamate excitotoxicity is the result of over activation of N-methyl-D-aspartate (NMDA) receptors. Therefore, modulating this receptor is a way to lessen some of the damaging effects of excess glutamate signaling. The FDA has approved memantine (e.g., Namenda®), an NMDA receptor blocker, for the treatment of moderate to severe Alzheimer's disease. Loss of Sex Hormones Evidence suggests that age-related loss of sex hormones – estrogen in women and testosterone in men – may contribute to Alzheimer's disease. Although the specific mechanisms are unclear, sex hormones appear to protect the brain against the development of Alzheimer's disease. For example, declining estrogen and testosterone levels seem to be associated with increased amyloid beta and tau abnormalities. Infections An intriguing theory that remains largely unappreciated by the medical community is that chronic infection with a variety of pathogenic bacteria and/ or viruses may contribute to the development of Alzheimer's disease. Research indicates that some common pathogens are consistently detected in the brains of Alzheimer's patients. For example, a comprehensive analysis of studies found that Spirochetes, a family of bacteria, was detected in about 90% of Alzheimer's patients and was virtually absent in healthy age-matched controls. Further statistical evaluation revealed a high probability of a causal relationship between Spirochetes infection and Alzheimer's disease. Spirochetes and other bacteria can linger in the brain and drive inflammation and the formation of amyloid beta and neurofibrillary tangles, all of which are hallmarks of Alzheimer's disease. Moreover, laboratory studies indicate that amyloid beta is an antimicrobial peptide, suggesting its formation could be an adaptive response to infectious organisms. These and other findings have led some researchers to hypothesize that "…early intervention against infection may delay or even prevent the future development of [Alzheimer's disease]".