Increased amyloid- levels in APPSWE transgenic mice treated chronically with a physiological high-fat high-cholesterol diet

Topic: Brain proteins, microglia and lab models

Although plasma cholesterol levels are not generally associated with Alzheimer disease (AD) incidence, in vitro studies have found that increased cellular cholesterol levels are associated with increases in -amyloid (A ) production, with a concomitant decrease in sAPPa, the secreted non amyloidogenic fragment of the amyloid precursor protein (APP). In two previous studies using a mouse model for AD-like pathology, non-physiological high-cholesterol diet has been shown to increase plasma and cerebral cholesterol levels, but have resulted in conflicting results on cerebral A levels. In the present study APPSWE male transgenic mice were fed either a chow diet or a physiological high-fat high-cholesterol Western-type diet until the mice reached 1 year of age. Mice fed the Western type diet, compared to the low-fat chow diet, had increased body weight, plasma and cerebral cholesterol levels, as well as a 50% increase in cerebral A levels. Cerebral levels of total APP were not altered while cerebral apoE levels were increased in the mice fed the Western-type diet, versus the chow-fed mice. These data demonstrate that chronic intake of a non-toxic high-cholesterol diet, which is similar to a human diet in fat and cholesterol content, was effective in increasing A levels and further suggests that dietary cholesterol and/or fat may be a risk factor for AD.

Key findings

• Although plasma cholesterol levels are not generally associated with Alzheimer disease (AD) incidence, in vitro studies have found that increased cellular cholesterol levels are associated with increases in -amyloid (A ) production, with a concomitant decrease in sAPPa, the secreted non amyloidogenic fragment of the amyloid precursor protein (APP).
• In two previous studies using a mouse model for AD-like pathology, non-physiological high-cholesterol diet has been shown to increase plasma and cerebral cholesterol levels, but have resulted in conflicting results on cerebral A levels.
• Mice fed the Western type diet, compared to the low-fat chow diet, had increased body weight, plasma and cerebral cholesterol levels, as well as a 50% increase in cerebral A levels.
• Cerebral levels of total APP were not altered while cerebral apoE levels were increased in the mice fed the Western-type diet, versus the chow-fed mice.
• These data demonstrate that chronic intake of a non-toxic high-cholesterol diet, which is similar to a human diet in fat and cholesterol content, was effective in increasing A levels and further suggests that dietary cholesterol and/or fat may be a risk factor for AD.

Why it matters

In this mouse study, a high-fat high-cholesterol diet increased cerebral amyloid-beta levels and apoE levels. It is an animal study and suggests dietary cholesterol and/or fat may be a risk factor, but does not show any treatment, cure, or prevention in people.

New to this subject? Start with our plain-English guide: Genetics →

Study details

• Evidence strengthLow

Read the original

• PubMed: 12474021
• Original source →

May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.

@article{levinallerhand2002-12474021,
  author  = {Levin-Allerhand, J. A. and Lominska, C. E. and Smith, J. D.},
  title   = {{Increased amyloid- levels in APPSWE transgenic mice treated chronically with a physiological high-fat high-cholesterol diet}},
  journal = {The journal of nutrition, health \& aging},
  year    = {2002},
  pmid    = {12474021}
}

Related studies in Genetics

• Anti-Inflammatory and Antiatherogenic Effects of the NLRP3 Inflammasome Inhibitor Arglabin in ApoE 2 .Ki Mice Fed a High-Fat Diet Circulation · 2015-03-24 · usefulness score 36/100
• Levels of soluble apolipoprotein E/amyloid-β (Aβ) complex are reduced and oligomeric Aβ increased with APOE4 and Alzheimer disease in a transgenic mouse model and human samples The Journal of biological chemistry · 2013-01-04 · usefulness score 50/100
• Brain apolipoprotein E levels in mice challenged by a Western diet increase in an allele-dependent manner Aging brain · 2023-11-27 · usefulness score 41/100
• Association of higher levels of high-density lipoprotein cholesterol in elderly individuals and lower risk of late-onset Alzheimer disease Archives of neurology · 2010-12-01 · usefulness score 55/100
• Genetic predisposition to increased blood cholesterol and triglyceride lipid levels and risk of Alzheimer disease: a Mendelian randomization analysis PLoS medicine · 2014-09-16 · usefulness score 62/100
• Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease Proceedings of the National Academy of Sciences of the United States of America · 1993-03-01 · usefulness score 58/100

Also tagged “amyloid-beta”

1,339 studies in the library carry the topic tag “amyloid-beta”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,339 tagged studies.

• Mapping the impact of age and APOE risk factors for late onset Alzheimer's disease on long range brain connections through multiscale bundle analysis Brain structure & function · 2025-03-20 · usefulness score 32/100 · Risk factors
• Transcriptomics and mechanistic elucidation of Alzheimer's disease risk genes in the brain and in vitro models Neurobiology of aging · 2014-09-06 · usefulness score 43/100 · TREM2 and immune genetics
• Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease PloS one · 2010-11-15 · usefulness score 56/100 · Brain tissue and pathology

Similar studies

• Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice 1996 · Laboratory science
• Genetic modification of the phenotypes produced by amyloid precursor protein overexpression in transgenic mice 1997 · Genetics
• Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology 1997 · Risk genes beyond APOE
• Profile of cholesterol-related sterols in aged amyloid precursor protein transgenic mouse brain 2002 · Risk genes beyond APOE
• Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease 2004 · Genetics
• Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death 2003 · Risk genes beyond APOE

More on Genetics

• A review that covers this ground Single and multiple transgenic mice as models for Alzheimer's disease Progress in neurobiology · 2000-06-01 · usefulness score 39/100
• Newest in this subject APH-1A and CDK5 Expression Correlates with Tau Hyperphosphorylation and Its Attenuation by Brahmi and Donep-M in STZ induced Alzheimer’s Disease Model Research Square · 2026-10-31 · Preprint — not yet peer-reviewed · usefulness score 16/100
• Newest in this subject Integrative systems biology identifies shared neuroimmune co-expression programmes across pulmonary tuberculosis and Alzheimer's disease Research Square · 2026-10-30 · Preprint — not yet peer-reviewed · usefulness score 16/100

See all studies in Genetics →