Poor Diet, Stress, and Inactivity Converge to Form a “Perfect Storm” That Drives Alzheimer’s Disease Pathogenesis

Abstract

North American incidence of Alzheimer’s disease (AD) is expected to more than double over the coming generation. Although genetic factors surrounding the production and clearance of amyloid-β and phosphorylated tau proteins are known to be responsible for a subset of early-onset AD cases, they do not explain the pathogenesis of the far more prevalent sporadic late-onset variant of the disease. It is thus likely that lifestyle and environmental factors contribute to neurodegenerative processes implicated in the pathogenesis of AD. Herein, we review evidence that (1) excess sucrose consumption induces AD-associated liver pathologies and brain insulin resistance, (2) chronic stress overdrives activity of locus coeruleus neurons, leading to loss of function (a common event in neurodegeneration), (3) high-sugar diets and stress promote the loss of neuroprotective sex hormones in men and women, and (4) Western dietary trends set the stage for a lithium-deficient state. We propose that these factors may intersect as part of a “perfect storm” to contribute to the widespread prevalence of neurodegeneration and AD. In addition, we put forth the argument that exercise and supplementation with trace lithium can counteract many of the deleterious consequences associated with excessive caloric intake and perpetual stress. We conclude that lifestyle and environmental factors likely contribute to AD pathogenesis and that simple lifestyle and dietary changes can help counteract their effects.

Suan-Zao-Ren Decoction ameliorates synaptic plasticity through inhibition of the Aβ deposition and JAK2/STAT3 signaling pathway in AD model of APP/PS1 transgenic mice

“…One typical pathological character of AD is the formation of senile plaques in the brain, which are induced by amyloid-β (Aβ) deposition and neurofibrillary tangles generated by exaggerated phosphorylation of tau protein within the neuron [8][9][10]. In addition, neuron loss and synaptic dysfunction mainly caused by senile plaques and neurofibrillary tangles are another crucial pathological feature of AD [11].…”

Traumatic stress history interacts with chronic peripheral inflammation to alter mitochondrial function of synaptosomes in a sex-specific manner

“…Males also showed an increase in pro-(IL-6, KC-GRO) and anti-(IL-5, IL-10) inflammatory peripheral cytokines after both the initial and final chronic injection of LPS. These effects are to be expected, as an initial immune challenge promotes the production and circulation of systemic inflammation in response to a challenge (Couper et al, 2008;Deslauriers et al, 2017;Pacholko et al, 2019;Pripp and Stanišić, 2014); however, the observed differences at the terminal endpoint suggest a more sustained impact on inflammatory regulation following chronic stress and chronic inflammation.…”

Examining the Role of the Noradrenergic Locus Coeruleus for Predicting Attention and Brain Maintenance in Healthy Old Age, Mild Cognitive Impairment and Alzheimer’s Disease: An MRI Structural Study On the Adni Cohort

“…Diet may also play a supportive role within the noradrenergic system as a preventing factor of neurodegenerative diseases. Indeed, poor and wrong diet-styles and their related neuroinflammatory consequences [140,141,142] are associated with worse prognosis and higher neurodegeneration risks [13, 140, 141 143, 144]. Interventions on diet may be beneficial to restore potential harmful micro and macro nutrient insufficiencies according to current guidelines for prevention [145].…”