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Neuroinflammatory mechanisms linking high‐fat diets to Alzheimer's disease vulnerability: Beyond the amyloid hypothesis
by
Barrientos, Ruth M.
, Mackey‐Alfonso, Sabrina E.
in
Alzheimer Disease - etiology
/ Alzheimer Disease - metabolism
/ Alzheimer Disease - pathology
/ Alzheimer's disease
/ Amyloid beta-Peptides - metabolism
/ Animals
/ Biomarkers
/ Body fat
/ Brain
/ Brain - metabolism
/ Brain - pathology
/ Brain health
/ Cognition
/ Cognitive impairment
/ complement system
/ Diet
/ Diet, High-Fat - adverse effects
/ Disease
/ Fats
/ FDA approval
/ high‐fat diet
/ Humans
/ Inflammation
/ Insulin
/ Life expectancy
/ Medical treatment
/ Memory
/ Neurodegeneration
/ neuroinflammation
/ Neuroinflammatory Diseases - metabolism
/ Obesity
/ Pathology
/ Preservation
/ Resistance
/ Review
/ synaptic loss
/ Toll-Like Receptor 4 - metabolism
/ toll‐like receptor 4
/ Vulnerability
2025
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Neuroinflammatory mechanisms linking high‐fat diets to Alzheimer's disease vulnerability: Beyond the amyloid hypothesis
by
Barrientos, Ruth M.
, Mackey‐Alfonso, Sabrina E.
in
Alzheimer Disease - etiology
/ Alzheimer Disease - metabolism
/ Alzheimer Disease - pathology
/ Alzheimer's disease
/ Amyloid beta-Peptides - metabolism
/ Animals
/ Biomarkers
/ Body fat
/ Brain
/ Brain - metabolism
/ Brain - pathology
/ Brain health
/ Cognition
/ Cognitive impairment
/ complement system
/ Diet
/ Diet, High-Fat - adverse effects
/ Disease
/ Fats
/ FDA approval
/ high‐fat diet
/ Humans
/ Inflammation
/ Insulin
/ Life expectancy
/ Medical treatment
/ Memory
/ Neurodegeneration
/ neuroinflammation
/ Neuroinflammatory Diseases - metabolism
/ Obesity
/ Pathology
/ Preservation
/ Resistance
/ Review
/ synaptic loss
/ Toll-Like Receptor 4 - metabolism
/ toll‐like receptor 4
/ Vulnerability
2025
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Do you wish to request the book?
Neuroinflammatory mechanisms linking high‐fat diets to Alzheimer's disease vulnerability: Beyond the amyloid hypothesis
by
Barrientos, Ruth M.
, Mackey‐Alfonso, Sabrina E.
in
Alzheimer Disease - etiology
/ Alzheimer Disease - metabolism
/ Alzheimer Disease - pathology
/ Alzheimer's disease
/ Amyloid beta-Peptides - metabolism
/ Animals
/ Biomarkers
/ Body fat
/ Brain
/ Brain - metabolism
/ Brain - pathology
/ Brain health
/ Cognition
/ Cognitive impairment
/ complement system
/ Diet
/ Diet, High-Fat - adverse effects
/ Disease
/ Fats
/ FDA approval
/ high‐fat diet
/ Humans
/ Inflammation
/ Insulin
/ Life expectancy
/ Medical treatment
/ Memory
/ Neurodegeneration
/ neuroinflammation
/ Neuroinflammatory Diseases - metabolism
/ Obesity
/ Pathology
/ Preservation
/ Resistance
/ Review
/ synaptic loss
/ Toll-Like Receptor 4 - metabolism
/ toll‐like receptor 4
/ Vulnerability
2025
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Neuroinflammatory mechanisms linking high‐fat diets to Alzheimer's disease vulnerability: Beyond the amyloid hypothesis
Journal Article
Neuroinflammatory mechanisms linking high‐fat diets to Alzheimer's disease vulnerability: Beyond the amyloid hypothesis
2025
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Overview
As global life expectancy increases, Alzheimer's disease (AD) incidence is rising rapidly. While research has long focused on amyloid beta (Aβ) and tau pathology, recent controversies and limited clinical success of Aβ‐targeting therapies have challenged their centrality in AD. Emerging evidence highlights neuroinflammation as an earlier and potentially more critical driver of disease, particularly in response to environmental and lifestyle factors. High saturated fat diets (HFD) are strongly associated with increased AD risk in both clinical and preclinical studies. This review examines how HFD promotes AD vulnerability via neuroinflammatory mechanisms, including toll‐like receptor 4 activation and complement system overactivation, which contribute to synaptic loss and cognitive decline—often independent of Aβ burden and metabolic dysfunction. Short‐term HFD exposure can rapidly induce neuroinflammation and impair memory, underscoring the direct impact of diet on brain health. These insights support a shift toward targeting immune pathways and synaptic preservation in AD prevention and treatment. Highlights High saturated fat diets (HFDs) increases Alzheimer's disease risk independently of obesity or insulin resistance. Neuroinflammation is a key driver of HFD‐induced cognitive decline. Toll‐like receptor 4 (TLR4) activation links saturated fats to synaptic loss and memory deficits. HFDs promote complement‐mediated microglial synaptic engulfment. Short‐term HFD exposure rapidly impairs memory and increases brain inflammation.
Publisher
John Wiley & Sons, Inc,Wiley
Subject
/ Alzheimer Disease - metabolism
/ Alzheimer Disease - pathology
/ Amyloid beta-Peptides - metabolism
/ Animals
/ Body fat
/ Brain
/ Diet
/ Diet, High-Fat - adverse effects
/ Disease
/ Fats
/ Humans
/ Insulin
/ Memory
/ Neuroinflammatory Diseases - metabolism
/ Obesity
/ Review
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