Alzheimer’s disease and insulin resistance: translating basic science into clinical applications

Felice, Fernanda G. De

doi:10.1172/jci64595

Cited by 285 publications

(222 citation statements)

References 128 publications

(160 reference statements)

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“…The prevalence of the disorder is increasing at an alarming rate, afflicting *30 million people worldwide and is expected to quadruple by 2050 [2]. The neuropathological characteristics of AD include the presence of senile plaques, defective brain insulin signaling [3], dysregulated cholesterol homeostasis [4], decreased glucose utilization, increased oxidative stress, and inflammation leading to neurodegeneration [5]. The plaques are composed mostly of aggregated amyloid-b 40 (Ab 40 ) and Ab 42 peptides, which are derived by proteolysis of the amyloid-b precursor protein (AbPP) [6,7].…”

Section: Introductionmentioning

confidence: 99%

Aβ-Induced Insulin Resistance and the Effects of Insulin on the Cholesterol Synthesis Pathway and Aβ Secretion in Neural Cells

et al. 2016

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Section: Introductionmentioning

confidence: 99%

Aβ-Induced Insulin Resistance and the Effects of Insulin on the Cholesterol Synthesis Pathway and Aβ Secretion in Neural Cells

et al. 2016

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“…Tg2576 mice also exhibit a recently recognized feature of mild cognitive impairment (MCI) and early AD: dysregulated insulin signaling (Abramov and Duchen, 2010;Agrawal and Gomez-Pinilla, 2012;De Felice, 2013). Peripheral insulin resistance is correlated with cognitive deficits in human AD (Talbot et al, 2012), a phenotype reflected in the Tg2576 model that also manifests as dysregulated CNS insulin signaling Denner et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Cognitive Enhancing Treatment with a PPARγ Agonist Normalizes Dentate Granule Cell Presynaptic Function in Tg2576 APP Mice

Nenov¹,

Laezza

Haidacher³

et al. 2014

J. Neurosci.

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Hippocampal network hyperexcitability is considered an early indicator of Alzheimer's disease (AD) memory impairment. Some AD mouse models exhibit similar network phenotypes. In this study we focused on dentate gyrus (DG) granule cell spontaneous and evoked properties in 9-month-old Tg2576 mice that model AD amyloidosis and cognitive deficits. Using whole-cell patch-clamp recordings, we found that Tg2576 DG granule cells exhibited spontaneous EPSCs that were higher in frequency but not amplitude compared with wild-type mice, suggesting hyperactivity of DG granule cells via a presynaptic mechanism. Further support of a presynaptic mechanism was revealed by increased I-O relationships and probability of release in Tg2576 DG granule cells.Since we and others have shown that activation of the peroxisome proliferator-activated receptor gamma (PPAR␥) axis improves hippocampal cognition in mouse models for AD as well as benefitting memory performance in some humans with early AD, we investigated how PPAR␥ agonism affected synaptic activity in Tg2576 DG. We found that PPAR␥ agonism normalized the I-O relationship of evoked EPSCs, frequency of spontaneous EPSCs, and probability of release that, in turn, correlated with selective expression of DG proteins essential for presynaptic SNARE function that are altered in patients with AD. These findings provide evidence that DG principal cells may contribute to early AD hippocampal network hyperexcitability via a presynaptic mechanism, and that hippocampal cognitive enhancement via PPAR␥ activation occurs through regulation of presynaptic vesicular proteins critical for proper glutamatergic neurotransmitter release, synaptic transmission, and short-term plasticity.

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“…Its insulin-reducing effect may decrease neoplastic growth of the prostate in humans [26]. Also, insulin resistance has been found to impair cognitive function [27] and to promote Alzheimer disease [28]. The association between lower urinary tract symptoms (LUTS) and risk of dementia [29] may relate to hyperinsulinemia as common pathogenic factor.…”

Section: Discussionmentioning

confidence: 99%

Treating Hyperinsulinemia with Momordica charantia

2015

J Metabolic Synd

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Objectives: To assess the efficacy of a novel nutraceutical mainly containing the extract of bitter gourd (Momordica charantia) and α-lipoic acid for the treatment of patients with hyperinsulinemia. Methods:Pilot prospective open-label cohort trial including 11 patients with hyperinsulinemia due to insulin resistance. The concentrations of insulin, C-peptide, glucose, haemoglobin A1c, total cholesterol, triglycerids, gamma-glutamyltransferase, and C-reactive protein were measured in blood take between 3 and 4 hours after dinner. Results:One and 4 months after initiation of treatment there was a significant decrease of the concentrations of Insulin (to average 25% of initial value), C-peptide (to average 44% of initial value), glucose, hemoglobin A1c and gamma-glutamyl transpeptidase.Clinical significance: Treatment of patients with hyperinsulinemia, with or without diabetes or metabolic syndrome, using a novel nutraceutical containing Momordica charantia and α-lipoic acid dramatically reduced insulin resistance and may have improved non-alcoholic fatty liver disease.

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Alzheimer’s disease and insulin resistance: translating basic science into clinical applications

Cited by 285 publications

References 128 publications

Aβ-Induced Insulin Resistance and the Effects of Insulin on the Cholesterol Synthesis Pathway and Aβ Secretion in Neural Cells

Aβ-Induced Insulin Resistance and the Effects of Insulin on the Cholesterol Synthesis Pathway and Aβ Secretion in Neural Cells

Cognitive Enhancing Treatment with a PPARγ Agonist Normalizes Dentate Granule Cell Presynaptic Function in Tg2576 APP Mice

Treating Hyperinsulinemia with Momordica charantia

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