Leptin Dysfunction and Alzheimer’s Disease: Evidence from Cellular, Animal, and Human Studies

McGuire, Matthew J.; Ishii, Makoto

doi:10.1007/s10571-015-0282-7

Cited by 90 publications

(84 citation statements)

References 141 publications

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“…The combined effects appear to lead to the predisposition of early‐onset AD in carriers of these alleles with obesity . Another mechanism by which obesity may increases the risk of AD is through alterations in leptin and inflammatory signalling in the central nervous system, which increase food intake, accumulation of β‐amyloid, and microvascular disease …”

Section: Obesity and Age‐related Diseasesmentioning

confidence: 99%

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Obesity and ageing: Two sides of the same coin

2020

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Summary Conditions and comorbidities of obesity mirror those of ageing and age‐related diseases. Obesity and ageing share a similar spectrum of phenotypes such as compromised genomic integrity, impaired mitochondrial function, accumulation of intracellular macromolecules, weakened immunity, shifts in tissue and body composition, and enhanced systemic inflammation. Moreover, it has been shown that obesity reduces life expectancy by 5.8 years in men and 7.1 years in women after the age of 40. Shorter life expectancy could be because obesity holistically accelerates ageing at multiple levels. Besides jeopardizing nuclear DNA and mitochondrial DNA integrity, obesity modifies the DNA methylation pattern, which is associated with epigenetic ageing in different tissues. Additionally, other signs of ageing are seen in individuals with obesity including telomere shortening, systemic inflammation, and functional declines. This review aims to show how obesity and ageing are “two sides of the same coin” through discussing how obesity predisposes an individual to age‐related conditions, illness, and disease. We will further demonstrate how the mechanisms that perpetuate the early‐onset of chronic diseases in obesity parallel those of ageing.

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Section: Obesity and Age‐related Diseasesmentioning

confidence: 99%

“…204,205 Another mechanism by which obesity may increases the risk of AD is through alterations in leptin and inflammatory signalling in the central nervous system, which increase food intake, accumulation of β-amyloid, and microvascular disease. [206][207][208]…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Obesity and ageing: Two sides of the same coin

2020

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“…More recently, adipokine's neuroprotective actions and their specific beneficial effects on memory have also been reported. Leptin is able to enhance hippocampal long-term potentiation and synaptic plasticity, as well as to promote non-amyloidogenic processing of amyloid-␤ protein precursor and prevent tau hyperphosphorylation [10]. On the contrary, a beneficial role of adiponectin in Alzheimer's disease natural history is still controversial, in spite of its recognized insulin-sensitizing, anti-inflammatory, anti-apoptotic, and anti-atherosclerotic properties [11] as well as recent reports of its capacity to promote dendritic growth, arborization, and spinogenesis in mature dentate gyrus neurons [12].…”

Section: Introductionmentioning

confidence: 99%

Association between Adipokines and Biomarkers of Alzheimer’s Disease: A Cross-Sectional Study

Letra

Matafome

Rodrigues

et al. 2019

JAD

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Background: Adipose tissue dysfunction has been implicated in the pathophysiology of Alzheimer's disease. However, the involvement of adipokines, particularly adiponectin, remains unclear. Objective: To compare serum and cerebrospinal fluid (CSF) levels of adiponectin, leptin and leptin-to-adiponectin ratio in patients within the spectrum of Alzheimer's disease and evaluate their relationship with classical biomarkers and their value as markers of progression. Methods: Amnestic mild cognitive impairment (MCI, n = 71) and Alzheimer's dementia (AD, n = 53) subjects were consecutively recruited for serum and CSF adiponectin and leptin determination using an analytically validated commercial enzyme-linked immunosorbent assay (ELISA). Correlations were explored using adjusted Spearman's correlation coefficients. A logistic regression model and ROC analysis were performed to evaluate the staging predictive value of adipokines. Results: Serum adiponectin was 33% higher in AD when compared to MCI patients. Adiponectin CSF levels, similar in both groups, were positively correlated with A␤ 42 and cognitive function, though only in women. The area under the ROC curve was 0.673 (95%CI:0.57-0.78) for serum adiponectin as predictor of dementia stage and the cutoff 10.85 g/ml maximized the sum of specificity (87%) and sensitivity (44%). Conclusion: Although longitudinal studies are required, we hypothesize that higher serum adiponectin in AD patients constitutes a strategy to compensate possible central signaling defects. In addition, adiponectin might be specifically assigned to neuroprotective functions in women and eventually involved in the female-biased incidence of Alzheimer's disease.

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“…Interestingly, although cord leptin served as an enhancer of gross motor development during the first 18 months of life, it was negatively associated with subscales of cognition at age 4 years (perceptual performance, executive function, working memory, and cognitive functions of the posterior cortex) and, more importantly, with general cognitive scores at both 4 and 6 years. Executive and memory functions require an optimal function of frontal, prefrontal, and temporal cortex and hippocampus structures (34); leptin, on the other hand, is an important regulator of hippocampal structure and function (35), and neonatal leptin deficiency was shown to reduce frontal cortex volume in a mouse model (36). Given the ability of leptin to cross the blood-brain barrier and act on its receptors (5), it is tempting to speculate that our findings could be attributed to the development of leptin resistance (37)(38)(39), promoted by hyperleptinemia during the critical time of fetal programming (40).…”

Section: Discussionmentioning

confidence: 99%

Cord Leptin is Associated with Neuropsychomotor Development in Childhood

Karakosta

Margetaki

Fthenou

et al. 2019

Obesity

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Objective Leptin is critical for central nervous system development and maturation. This study aimed to evaluate the potential regulatory role of cord leptin in the neuropsychomotor development of children ages 18 months to 6 years. Methods This study included 424 children from a prospective mother‐child cohort (Rhea Study; Crete, Greece) with available cord leptin levels and data on neurodevelopmental outcomes at 18 months (Bayley Scales of Infant and Toddler Development, Third Edition), 4 years (McCarthy Scales of Children's Abilities), and 6 years (Raven's Coloured Progressive Matrices and Trail Making Test). Multivariable linear regression models were used to explore the associations. Results Each 10‐ng/mL increase in the cord leptin level was associated with increased scores on the gross motor scale at 18 months (β coefficient: 3.8; 95% CI: 0.0‐7.5), with decreased scores in the general cognitive performance (β coefficient: −3.0; 95% CI: −5.5 to −0.4), perceptual performance (β coefficient: −3.4; 95% CI: −6.0 to −9.9), working memory (β coefficient: −3.1; 95% CI: −5.7 to −0.4), executive function (β coefficient −3.1; 95% CI: −5.7 to −0.5), and functions of the posterior cortex (β coefficient: −2.7; 95% CI: −5.2 to −0.1) scales at 4 years, and with a 3.7‐unit decrease in the Raven's Coloured Progressive Matrices score at 6 years (β coefficient: −3.7; 95% CI: −6.9 to −0.5). Conclusions Increased cord leptin levels are associated with enhanced gross motor development at 18 months but decreased cognitive performance in early and middle childhood.

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Leptin Dysfunction and Alzheimer’s Disease: Evidence from Cellular, Animal, and Human Studies

Cited by 90 publications

References 141 publications

Obesity and ageing: Two sides of the same coin

Obesity and ageing: Two sides of the same coin

Association between Adipokines and Biomarkers of Alzheimer’s Disease: A Cross-Sectional Study

Cord Leptin is Associated with Neuropsychomotor Development in Childhood

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