The DOI matches its Crossref record; 326 of the 328 references it cites were found in a registry or an index.
Western diet as a trigger of Alzheimer’s disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration
Open accessAbstract
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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“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.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [643]
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“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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1 retracted
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RetractedObesity is associated with macrophage accumulation in adipose tissue
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Dementia prevention, intervention, and care
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Host microbiota constantly control maturation and function of microglia in the CNS
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193
Dominguez, L. J., Veronese, N., Vernuccio, L., Catanese, G., Inzerillo, F., Salemi, G., & Barbagallo, M. (2021) · Nutrients · doi:10.3390/nu13114080 · Cited by 433
Pathogenesis of Alzheimer’s Disease
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The gut microbiome in Alzheimer’s disease: what we know and what remains to be explored
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Gene–environment interactions in Alzheimer disease: the emerging role of epigenetics
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Metadata
- Authors
- Więckowska-Gacek, A., Mietelska-Porowska, A., Wydrych, M., & Wojda, U.
- Affiliations
- Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
- Venue
- Ageing Research Reviews
- Publisher
- Elsevier BV
- Published
- 2021-09
- Volume
- 70
- Pages
- 101397
- ISSN
- 1568-1637 (ISSN-L)
- 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
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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