Exploiting Common Aspects of Obesity and Alzheimer's Disease

Overview

Journal Front Hum Neurosci

Specialty Neurology

Date 2021 Jan 1

PMID 33384592

Citations 18

Authors

Sidra Tabassum

Afzal Misrani

Li Yang

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease (AD) is an example of age-related dementia, and there are still no known preventive or curative measures for this disease. Obesity and associated metabolic changes are widely accepted as risk factors of age-related cognitive decline. Insulin is the prime mediator of metabolic homeostasis, which is impaired in obesity, and this impairment potentiates amyloid-β (Aβ) accumulation and the formation of neurofibrillary tangles (NFTs). Obesity is also linked with functional and morphological alterations in brain mitochondria leading to brain insulin resistance (IR) and memory deficits associated with AD. Also, increased peripheral inflammation and oxidative stress due to obesity are the main drivers that increase an individual's susceptibility to cognitive deficits, thus doubling the risk of AD. This enhanced risk of AD is alarming in the context of a rapidly increasing global incidence of obesity and overweight in the general population. In this review, we summarize the risk factors that link obesity with AD and emphasize the point that the treatment and management of obesity may also provide a way to prevent AD.

Citing Articles

Adiponectin deficiency is a critical factor contributing to cognitive dysfunction in obese mice after sevoflurane exposure.

Chu J, Chiu S, Wang J, Chang R, Chun Wong G Mol Med. 2024; 30(1):177.

PMID: 39415089 PMC: 11481458. DOI: 10.1186/s10020-024-00954-0.

Leptin bioavailability and markers of brain atrophy and vascular injury in the middle age.

Charisis S, Short M, Bernal R, Kautz T, Trevino H, Mathews J Alzheimers Dement. 2024; 20(9):5849-5860.

PMID: 39132759 PMC: 11497668. DOI: 10.1002/alz.13879.

Association between increased BMI and cognitive function in first-episode drug-naïve male schizophrenia.

Deng X, Lu S, Li Y, Fang X, Zhang R, Shen X Front Psychiatry. 2024; 15:1362674.

PMID: 38505798 PMC: 10948420. DOI: 10.3389/fpsyt.2024.1362674.

Mechanisms of 3-Hydroxyl 3-Methylglutaryl CoA Reductase in Alzheimer's Disease.

Zhou X, Wu X, Wang R, Han L, Li H, Zhao W Int J Mol Sci. 2024; 25(1).

PMID: 38203341 PMC: 10778631. DOI: 10.3390/ijms25010170.

Feeding High-Fat Diet Accelerates Development of Peripheral and Central Insulin Resistance and Inflammation and Worsens AD-like Pathology in APP/PS1 Mice.

Mengr A, Strnadova V, Strnad S, Vrkoslav V, Pelantova H, Kuzma M Nutrients. 2023; 15(17).

PMID: 37686722 PMC: 10490051. DOI: 10.3390/nu15173690.

References

Cardoso A, Cabral-Costa J, Kowaltowski A . Effects of a high fat diet on liver mitochondria: increased ATP-sensitive K+ channel activity and reactive oxygen species generation. J Bioenerg Biomembr. 2010; 42(3):245-53. DOI: 10.1007/s10863-010-9284-9. View

Freude S, Plum L, Schnitker J, Leeser U, Udelhoven M, Krone W . Peripheral hyperinsulinemia promotes tau phosphorylation in vivo. Diabetes. 2005; 54(12):3343-8. DOI: 10.2337/diabetes.54.12.3343. View

Nuzzo D, Picone P, Baldassano S, Caruana L, Messina E, Marino Gammazza A . Insulin Resistance as Common Molecular Denominator Linking Obesity to Alzheimer's Disease. Curr Alzheimer Res. 2015; 12(8):723-35. DOI: 10.2174/1567205012666150710115506. View

Saltiel A, Olefsky J . Inflammatory mechanisms linking obesity and metabolic disease. J Clin Invest. 2017; 127(1):1-4. PMC: 5199709. DOI: 10.1172/JCI92035. View

Roth R, Le A, Zhang L, Kahn M, Samuel V, Shulman G . MAPK phosphatase-1 facilitates the loss of oxidative myofibers associated with obesity in mice. J Clin Invest. 2009; 119(12):3817-29. PMC: 2786792. DOI: 10.1172/JCI39054. View

Halagappa V, Guo Z, Pearson M, Matsuoka Y, Cutler R, LaFerla F . Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease. Neurobiol Dis. 2007; 26(1):212-20. DOI: 10.1016/j.nbd.2006.12.019. View

Dragicevic N, Mamcarz M, Zhu Y, Buzzeo R, Tan J, Arendash G . Mitochondrial amyloid-beta levels are associated with the extent of mitochondrial dysfunction in different brain regions and the degree of cognitive impairment in Alzheimer's transgenic mice. J Alzheimers Dis. 2010; 20 Suppl 2:S535-50. DOI: 10.3233/JAD-2010-100342. View

Leuner B, Max M, Thamm K, Kausler C, Yakobus Y, Bierhaus A . RAGE influences obesity in mice. Effects of the presence of RAGE on weight gain, AGE accumulation, and insulin levels in mice on a high fat diet. Z Gerontol Geriatr. 2012; 45(2):102-8. DOI: 10.1007/s00391-011-0279-x. View

Liu X, Hajnoczky G . Altered fusion dynamics underlie unique morphological changes in mitochondria during hypoxia-reoxygenation stress. Cell Death Differ. 2011; 18(10):1561-72. PMC: 3172112. DOI: 10.1038/cdd.2011.13. View

10.

Bartos A, Fialova L, Svarcova J, Ripova D . Patients with Alzheimer disease have elevated intrathecal synthesis of antibodies against tau protein and heavy neurofilament. J Neuroimmunol. 2012; 252(1-2):100-5. DOI: 10.1016/j.jneuroim.2012.08.001. View

11.

Ahmad T, Aggarwal K, Pattnaik B, Mukherjee S, Sethi T, Tiwari B . Computational classification of mitochondrial shapes reflects stress and redox state. Cell Death Dis. 2013; 4:e461. PMC: 3564000. DOI: 10.1038/cddis.2012.213. View

12.

Bombicino S, Iglesias D, Rukavina-Mikusic I, Buchholz B, Gelpi R, Boveris A . Hydrogen peroxide, nitric oxide and ATP are molecules involved in cardiac mitochondrial biogenesis in Diabetes. Free Radic Biol Med. 2017; 112:267-276. DOI: 10.1016/j.freeradbiomed.2017.07.027. View

13.

Gasparini L, Gouras G, Wang R, GROSS R, Beal M, Greengard P . Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling. J Neurosci. 2001; 21(8):2561-70. PMC: 6762523. View

14.

Ji J, Qin Y, Ren J, Lu C, Wang R, Dai X . Mitochondria-related miR-141-3p contributes to mitochondrial dysfunction in HFD-induced obesity by inhibiting PTEN. Sci Rep. 2015; 5:16262. PMC: 4637860. DOI: 10.1038/srep16262. View

15.

Mattson M, Gleichmann M, Cheng A . Mitochondria in neuroplasticity and neurological disorders. Neuron. 2008; 60(5):748-66. PMC: 2692277. DOI: 10.1016/j.neuron.2008.10.010. View

16.

Nistico R, Cavallucci V, Piccinin S, Macri S, Pignatelli M, Mehdawy B . Insulin receptor β-subunit haploinsufficiency impairs hippocampal late-phase LTP and recognition memory. Neuromolecular Med. 2012; 14(4):262-9. DOI: 10.1007/s12017-012-8184-z. View

17.

Karmi A, Iozzo P, Viljanen A, Hirvonen J, Fielding B, Virtanen K . Increased brain fatty acid uptake in metabolic syndrome. Diabetes. 2010; 59(9):2171-7. PMC: 2927939. DOI: 10.2337/db09-0138. View

18.

Choudhary S, Sinha S, Zhao Y, Banerjee S, Sathyanarayana P, Shahani S . NF-kappaB-inducing kinase (NIK) mediates skeletal muscle insulin resistance: blockade by adiponectin. Endocrinology. 2011; 152(10):3622-7. PMC: 3176647. DOI: 10.1210/en.2011-1343. View

19.

Cao D, Lu H, Lewis T, Li L . Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease. J Biol Chem. 2007; 282(50):36275-82. DOI: 10.1074/jbc.M703561200. View

20.

Kim S, Reaven G . Insulin resistance and hyperinsulinemia: you can't have one without the other. Diabetes Care. 2008; 31(7):1433-8. PMC: 2453638. DOI: 10.2337/dc08-0045. View