Obesity as a risk factor for Alzheimer’s disease: the role of adipocytokines

Abstract

Alzheimer's disease is the leading cause of dementia and the most prevalent neurodegenerative disease. It is an aging-related multi-factorial disorder and growing evidence support the contribution of metabolic factors to what was formerly thought to be a centrally mediated process. Obesity has already been recognized as an important player in the pathogenesis of this type of dementia, independently of insulin resistance or other vascular risk factors. Although the exact underlying mechanisms are still unknown, adipocyte dysfunction and concomitant alteration in adipocyte-derived protein secretion seem to be involved, since these adipocytokines can cross the blood-brain barrier and influence cognitive-related structures. Very few studies have assessed the role of adipocytokines dysfunction on cognitive impaired patients and yielded contradictory results. Interestingly, extensive research on the central effects of leptin in Alzheimer's diseasetransgenic mice has demonstrated its capacity to enhance synaptic plasticity and strength, as well as to prevent betaamyloid deposition and tau phosphorylation. In addition, adiponectin, the most abundant adipocytokine whose levels are inversely correlated to adiposity, has shown to be neuroprotective to hippocampal cells. Many other adipose-derived cytokines have mainly pro-inflammatory properties, being able to trigger and/or enhance central inflammatory cascades and also to influence the secretion of other adipocytokines involved in cognition. This paper pretends to review the existing evidence on the contribution of adipocytokines dysfunction to the increased risk of dementia associated with midlife obesity, unraveling its insulin-independent effects on cognition.

Weight loss is associated with improvements in cognitive function among overweight and obese people: A systematic review and meta-analysis

“…Inflammation and oxidative stress seem to play a pivotal role in the pathogenesis of cognitive decline (Bennett et al, 2009;Schmidt et al, 2002). Moreover, in Alzheimer's disease-transgenic mice adiponectin has been shown to be neuroprotective for hippocampal cells (Letra et al, 2014). Therefore, the modulation of these cytokines and adipokines through weight loss could contribute, at least in part, to the improvement in the cognitive tests observed in the treated subjects, and influence brain function and structure in obese and overweight subjects (Bischof and Park, 2015).…”

Insulin Resistance as Common Molecular Denominator Linking Obesity to Alzheimer’s Disease

“…Hence, monitoring of APP expression and processing in peripheral tissues could provide a checkpoint both for AD and obesity development and progression. Increase of APP gene expression may be correlated with insulin resistance and pro-inflammatory and adipocytokine gene expression [38,39]. Insulin resistance, defined as a lower than expected response to a given dose of insulin, is a pathological condition characteristic of metabolic disorders as T2D, obesity and pathology related to aging [36].…”

Influence of Obstructive Sleep Apnea Syndrome and Sleep Variables on Cognitive Performance and Psychological Distress in Severely Obese Patients

“…Obesity is also linked to neuropsychological impairment, namely, reduction in attention, learning, memory and executive functions and might be an additional risk factor for neurodegenerative disease such as Alzheimer's disease (Letra, Santana, & Seiç a, 2014;Ribeiro et al, 2015;Stanek et al, 2011).…”