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Western diet as a trigger of Alzheimer's disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration.
Ageing Res Rev. 2021 09; 70:101397.AR

Abstract

An excess of saturated fatty acids and simple sugars in the diet is a known environmental risk factor of Alzheimer's disease (AD) but the holistic view of the interacting processes through which such diet may contribute to AD pathogenesis is missing. We addressed this need through extensive analysis of published studies investigating the effects of western diet (WD) on AD development in humans and laboratory animals. We reviewed WD-induced systemic alterations comprising metabolic changes, induction of obesity and adipose tissue inflammation, gut microbiota dysbiosis and acceleration of systemic low-grade inflammation. Next we provide an overview of the evidence demonstrating that WD-associated systemic alterations drive impairment of the blood-brain barrier (BBB) and development of neuroinflammation paralleled by accumulation of toxic amyloid. Later these changes are followed by dysfunction of synaptic transmission, neurodegeneration and finally memory and cognitive impairment. We conclude that WD can trigger AD by acceleration of inflammaging, and that BBB impairment induced by metabolic and systemic inflammation play the central role in this process. Moreover, the concurrence of neuroinflammation and Aβ dyshomeostasis, which by reciprocal interactions drive the vicious cycle of neurodegeneration, contradicts Aβ as the primary trigger of AD. Given that in 2019 the World Health Organization recommended focusing on modifiable risk factors in AD prevention, this overview of the sequential, complex pathomechanisms initiated by WD, which can lead from peripheral disturbances to neurodegeneration, can support future prevention strategies.

Authors+Show Affiliations

Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093 Warsaw, Poland.Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093 Warsaw, Poland.Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093 Warsaw, Poland.Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093 Warsaw, Poland. Electronic address: u.wojda@nencki.edu.pl.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

34214643

Citation

Więckowska-Gacek, Angelika, et al. "Western Diet as a Trigger of Alzheimer's Disease: From Metabolic Syndrome and Systemic Inflammation to Neuroinflammation and Neurodegeneration." Ageing Research Reviews, vol. 70, 2021, p. 101397.
Więckowska-Gacek A, Mietelska-Porowska A, Wydrych M, et al. Western diet as a trigger of Alzheimer's disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration. Ageing Res Rev. 2021;70:101397.
Więckowska-Gacek, A., Mietelska-Porowska, A., Wydrych, M., & Wojda, U. (2021). Western diet as a trigger of Alzheimer's disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration. Ageing Research Reviews, 70, 101397. https://doi.org/10.1016/j.arr.2021.101397
Więckowska-Gacek A, et al. Western Diet as a Trigger of Alzheimer's Disease: From Metabolic Syndrome and Systemic Inflammation to Neuroinflammation and Neurodegeneration. Ageing Res Rev. 2021;70:101397. PubMed PMID: 34214643.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Western diet as a trigger of Alzheimer's disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration. AU - Więckowska-Gacek,Angelika, AU - Mietelska-Porowska,Anna, AU - Wydrych,Małgorzata, AU - Wojda,Urszula, Y1 - 2021/06/30/ PY - 2021/03/23/received PY - 2021/06/10/revised PY - 2021/06/24/accepted PY - 2021/7/3/pubmed PY - 2021/9/11/medline PY - 2021/7/2/entrez KW - Alzheimer’s disease KW - Blood-brain barrier impairment KW - Gut-brain axis KW - Metabolic syndrome KW - Neurodegeneration KW - Neuroinflammation KW - Obesity KW - Pathogenesis SP - 101397 EP - 101397 JF - Ageing research reviews JO - Ageing Res Rev VL - 70 N2 - An excess of saturated fatty acids and simple sugars in the diet is a known environmental risk factor of Alzheimer's disease (AD) but the holistic view of the interacting processes through which such diet may contribute to AD pathogenesis is missing. We addressed this need through extensive analysis of published studies investigating the effects of western diet (WD) on AD development in humans and laboratory animals. We reviewed WD-induced systemic alterations comprising metabolic changes, induction of obesity and adipose tissue inflammation, gut microbiota dysbiosis and acceleration of systemic low-grade inflammation. Next we provide an overview of the evidence demonstrating that WD-associated systemic alterations drive impairment of the blood-brain barrier (BBB) and development of neuroinflammation paralleled by accumulation of toxic amyloid. Later these changes are followed by dysfunction of synaptic transmission, neurodegeneration and finally memory and cognitive impairment. We conclude that WD can trigger AD by acceleration of inflammaging, and that BBB impairment induced by metabolic and systemic inflammation play the central role in this process. Moreover, the concurrence of neuroinflammation and Aβ dyshomeostasis, which by reciprocal interactions drive the vicious cycle of neurodegeneration, contradicts Aβ as the primary trigger of AD. Given that in 2019 the World Health Organization recommended focusing on modifiable risk factors in AD prevention, this overview of the sequential, complex pathomechanisms initiated by WD, which can lead from peripheral disturbances to neurodegeneration, can support future prevention strategies. SN - 1872-9649 UR - https://www.unboundmedicine.com/medline/citation/34214643/Western_diet_as_a_trigger_of_Alzheimer's_disease:_From_metabolic_syndrome_and_systemic_inflammation_to_neuroinflammation_and_neurodegeneration_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1568-1637(21)00144-6 DB - PRIME DP - Unbound Medicine ER -