Western diet as a trigger of Alzheimer's disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration
- PMID: 34214643
- DOI: 10.1016/j.arr.2021.101397
Western diet as a trigger of Alzheimer's disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration
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.
Keywords: Alzheimer’s disease; Blood-brain barrier impairment; Gut-brain axis; Metabolic syndrome; Neurodegeneration; Neuroinflammation; Obesity; Pathogenesis.
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.
Similar articles
-
Western Diet Induces Impairment of Liver-Brain Axis Accelerating Neuroinflammation and Amyloid Pathology in Alzheimer's Disease.Front Aging Neurosci. 2021 Apr 1;13:654509. doi: 10.3389/fnagi.2021.654509. eCollection 2021. Front Aging Neurosci. 2021. PMID: 33867971 Free PMC article.
-
Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease.Life Sci. 2021 Jan 1;264:118627. doi: 10.1016/j.lfs.2020.118627. Epub 2020 Oct 22. Life Sci. 2021. PMID: 33169684 Review.
-
White matter inflammation and cognitive function in a co-morbid metabolic syndrome and prodromal Alzheimer's disease rat model.J Neuroinflammation. 2020 Jan 21;17(1):29. doi: 10.1186/s12974-020-1698-7. J Neuroinflammation. 2020. PMID: 31964387 Free PMC article.
-
Worsening of memory deficit induced by energy-dense diet in a rat model of early-Alzheimer's disease is associated to neurotoxic Aβ species and independent of neuroinflammation.Biochim Biophys Acta Mol Basis Dis. 2017 Mar;1863(3):731-743. doi: 10.1016/j.bbadis.2016.12.014. Epub 2016 Dec 27. Biochim Biophys Acta Mol Basis Dis. 2017. PMID: 28039031
-
Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer's disease.J Neurosci Res. 2017 Apr;95(4):943-972. doi: 10.1002/jnr.23777. Epub 2016 Jun 27. J Neurosci Res. 2017. PMID: 27350397 Review.
Cited by
-
Sex-dependent effects of carbohydrate source and quantity on caspase-1 activity in the mouse central nervous system.J Neuroinflammation. 2024 Jun 5;21(1):151. doi: 10.1186/s12974-024-03140-5. J Neuroinflammation. 2024. PMID: 38840215 Free PMC article.
-
The microbiota-gut-brain-immune interface in the pathogenesis of neuroinflammatory diseases: a narrative review of the emerging literature.Front Immunol. 2024 May 16;15:1365673. doi: 10.3389/fimmu.2024.1365673. eCollection 2024. Front Immunol. 2024. PMID: 38817603 Free PMC article. Review.
-
Deciphering molecular bridges: Unveiling the interplay between metabolic syndrome and Alzheimer's disease through a systems biology approach and drug repurposing.PLoS One. 2024 May 29;19(5):e0304410. doi: 10.1371/journal.pone.0304410. eCollection 2024. PLoS One. 2024. PMID: 38809924 Free PMC article.
-
Bridging metabolic syndrome and cognitive dysfunction: role of astrocytes.Front Endocrinol (Lausanne). 2024 May 10;15:1393253. doi: 10.3389/fendo.2024.1393253. eCollection 2024. Front Endocrinol (Lausanne). 2024. PMID: 38800473 Free PMC article. Review.
-
Western diet increases brain metabolism and adaptive immune responses in a mouse model of amyloidosis.J Neuroinflammation. 2024 May 14;21(1):129. doi: 10.1186/s12974-024-03080-0. J Neuroinflammation. 2024. PMID: 38745337 Free PMC article.
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Medical