Early multidomain intervention to stave off Alzheimer’s disease

Abstract

Alzheimer’s disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually the ability to carry out the simplest tasks. In most people with Alzheimer’s symptoms first appear in their mid-60s. The typical lesions of Alzheimer’s disease (AD) feature in cognitive impairment, amyloid β (A β ) deposits (senile plaque), hyperphosphorylation of Tau in neurofibrillary tangles (NTFs), glial cells activation and cerebral atrophy. The plaques and tangles in the brain are considered to be the main features of Alzheimer’s disease. Loss of connections between neurons in the brain deteriorates neuronal message transmission between different parts of the brain, and from the brain to muscles and organs in the body. Over one hundred years, a great deal of research has been focused on the dementia of clinical phase, and on single-target drugs to intervene the progression of AD. However, a real breakthrough in the treatment still needs to be made to stave off AD. Currently, to clarify early pathological changes of pre-clinical stage is imperative to understand AD. Although aging, family history and susceptibility genes have been considered to be the most important factors, the rapid increase of AD patients does not conform to Hardy-Weinberg equilibrium. Therefore, environmental factors are more important than genetic factors in AD. The onset of human metabolic disorders becomes more related and vulnerable to endogenous and exogenous environmental pathogenic factors than genetics. Different environmental factors had been found to disrupt the binding affinity of Tau to microtubules or DNA, and to diminish the stability of its cellular skeleton by inducing Tau phosphorylation and amyloid β deposition. For example, five year-old monkeys (Macaca mulatta) which were administrated with low concentrations of methanol for 2 years and suffered from senile plaque, A β deposits, neurofibrillary like-tangles in parietal lobe and hippocampus. However, the direct relation between these environmental factors and neurodegenerative diseases is still waiting to be clarified. In order to stave off the onset and progression of AD, different interventions are emphasized and applied in AD treatments, such as developing multiple targeting drugs, ameliorating lifestyle, regulating diet, providing music care, attending physical exercises, and participating in social activities. Chronic dehydration is regarded as a common symptom of patients with age-related cognitive impairment, particularly those with Alzheimer disease. Chronic dehydration in mice results in dysregulation of brain formaldehyde, which decreases the level of 5-HT and slows learning in shuttle box. Establishing good water intake habits not only effectively eliminates excess formaldehyde and other metabolic products but also yields valuable approaches to reducing the risk of AD prior to the onset of the disease. The multidomain intervention will be one of comprehensive therapies for AD patients, especially for those in preclinical phase.