Western diet as a trigger of Alzheimer’s disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration

Więckowska-Gacek, Angelika; Mietelska-Porowska, Anna; Wydrych, Małgorzata; Wojda, Urszula

doi:10.1016/j.arr.2021.101397

Cited by 346Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Western diet as a trigger of Alzheimer’s disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration

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Więckowska-Gacek, Angelika, Mietelska-Porowska, Anna, Wydrych, Małgorzata, Wojda, Urszula·2021·Ageing Research Reviews

DOI 10.1016/j.arr.2021.101397

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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.

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Increased intestinal permeability facilitates the translocation of bacteria and their byproducts into the mucosa and bloodstream, leading to aberrant activation of intestinal and circulating immune and inflammatory cells, resulting in systemic inflammation, neuroinflammation, and neurodegeneration.
“the increased intestinal permeability facilitates the translocation of bacteria and their byproducts into the mucosa and bloodstream. This leads to aberrant activation of the intestinal and circulating immune and inflammatory cells, resulting in systemic inflammation, neuroinflammation, and neurodegeneration.”
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Systemic inflammation may disrupt the BBB, allowing pro-inflammatory molecules to enter the CNS.
“According to previous studies, systemic inflammation may disrupt the BBB, allowing pro-inflammatory molecules (such as cytokines and LPS) to enter the CNS [60,61,62].”
From Neuroprotective Effects of Bifidobacterium breve CCFM1067 in MPTP-Induced Mouse Models of Parkinson’s Disease (2022) · cites this paper as [62]

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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
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Natural Aporphine Alkaloids with Potential to Impact Metabolic Syndrome
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Gut microbiota short-chain fatty acids and their impact on the host thyroid function and diseases
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Alzheimer’s disease pathogenesis: standing at the crossroad of lipid metabolism and immune response
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Rinoldi, C., Ziai, Y., Zargarian, S. S., Nakielski, P., Zembrzycki, K., Bayan, M. A. H., Zakrzewska, A., Fiorelli, R., Lanzi, M., Kostrzewska-Księżyk, A., et al. (2022) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.2c17025 · Cited by 47 · see citing works
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The role of intestinal microbiota and metabolites in intestinal inflammation
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Western diet consumption impairs memory function via dysregulated hippocampus acetylcholine signaling
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Pterostilbene could alleviate diabetic cognitive impairment by suppressing TLR4/NF‐кB pathway through microbiota‐gut‐brain axis
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Gut-brain axis: gut dysbiosis and psychiatric disorders in Alzheimer’s and Parkinson’s disease
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Authors: Więckowska-Gacek, A., Mietelska-Porowska, A., Wydrych, M., & Wojda, U.
Affiliations: Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
ORCID: Więckowska-Gacek, Angelika
Mietelska-Porowska, Anna
Wydrych, Małgorzata
Wojda, Urszula
Venue: Ageing Research Reviews
Publisher: Elsevier BV
Published: 2021-09
Volume: 70
Pages: 101397
ISSN: 1568-1637 (ISSN-L)
DOI: 10.1016/j.arr.2021.101397
OpenAlex: W3174384278
Cited by: 343
References: 328
Citations by year: 2026: 53 · 2025: 75 · 2024: 92 · 2023: 71 · 2022: 43 · 2021: 9
FWCI: 7.27
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: Ageing Research Reviews (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Funders: Narodowe Centrum Nauki (UMO-2014/15/D/NZ4/04361, UMO-2018/29/N/NZ7/01724)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: Western diet, Alzheimer's disease, metabolic syndrome, systemic inflammation, neuroinflammation, neurodegeneration, blood-brain barrier, amyloid-beta, inflammaging, gut dysbiosis, obesity, adipose tissue inflammation, synaptic dysfunction, memory impairment, cognitive impairment, dietary saturated fatty acids, sugar consumption, modifiable risk factors
MeSH terms: Alzheimer Disease, Animals, Humans, Inflammation, Metabolic Syndrome, Cognitive Dysfunction, Diet, Western

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Western diet as a trigger of Alzheimer’s disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration

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