Single and multiple transgenic mice as models for Alzheimer's disease

Topic: Amyloid, tau and blood-test diagnosis

Transgenic mice expressing in brain different mutant forms of the Amyloid Precursor Protein, develop functional, cognitive and pathological defects which resemble or are reminiscent of symptoms observed in Alzheimer's disease (AD) patients. The late development of amyloid plaques in aging transgenic APP mice is needed to warrant that the earlier behavioural and cognitive defects are informative for the human disorder. We describe and discuss our work, the rationale behind the approach and the techniques used to generate these APP transgenic mice, including specific experimental problems. The APP transgenic mouse models are being comprehensively characterized and offer excellent perspectives for the study and definition of early biochemical and pathological aspects that are not accessible in human AD patients. The ongoing combination by breeding with other transgenic mouse strains, i.e. mice overexpressing human Presenilin 1, ApoE 4 and protein tau to generate "multiple" transgenic mice, offer additional potential to define the pathological interactions of these genetic factors, known to be involved, directly or indirectly, in dementia of the Alzheimer type. Finally, it must be the aim to obtain transgenic mice that not only model amyloidogenesis, but also the neurofibrillary tangle pathology and the involvement of protein tau.

Key findings

• The late development of amyloid plaques in aging transgenic APP mice is needed to warrant that the earlier behavioural and cognitive defects are informative for the human disorder.
• We describe and discuss our work, the rationale behind the approach and the techniques used to generate these APP transgenic mice, including specific experimental problems.
• The APP transgenic mouse models are being comprehensively characterized and offer excellent perspectives for the study and definition of early biochemical and pathological aspects that are not accessible in human AD patients.
• The ongoing combination by breeding with other transgenic mouse strains, i.e. mice overexpressing human Presenilin 1, ApoE 4 and protein tau to generate "multiple" transgenic mice, offer additional potential to define the pathological interactions of these genetic factors, known to be involved, directly or indirectly, in dementia of the Alzheimer type.
• Finally, it must be the aim to obtain transgenic mice that not only model amyloidogenesis, but also the neurofibrillary tangle pathology and the involvement of protein tau.

Why it matters

This paper describes transgenic mice that express mutant forms of the amyloid precursor protein and develop cognitive and pathological features resembling Alzheimer's disease. These animal models are useful for studying early biochemical and pathological aspects not accessible in human patients, and breeding them with other strains may help define how genetic factors interact, but this is animal research.

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Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/s0301-0082(99)00055-6
• PubMed: 10727777
• 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{vanleuven2000-10727777,
  author  = {van Leuven, F.},
  title   = {{Single and multiple transgenic mice as models for Alzheimer's disease}},
  journal = {Progress in neurobiology},
  year    = {2000},
  doi     = {10.1016/s0301-0082(99)00055-6},
  pmid    = {10727777},
  url     = {https://doi.org/10.1016/s0301-0082(99)00055-6}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice Science · 1996-10-04 · usefulness score 62/100 · Laboratory science
• Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein Nature · 1995-02-01 · usefulness score 59/100 · Risk genes beyond APOE
• Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes Nature medicine · 1998-01-01 · usefulness score 58/100 · Risk genes beyond APOE
• Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins Neuron · 1997-10-01 · usefulness score 53/100 · Risk genes beyond APOE
• Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology Proceedings of the National Academy of Sciences of the United States of America · 1997-11-01 · usefulness score 52/100 · Risk genes beyond APOE
• Amyloid precursor protein processing and A beta42 deposition in a transgenic mouse model of Alzheimer disease Proceedings of the National Academy of Sciences of the United States of America · 1997-02-01 · usefulness score 48/100 · Risk genes beyond APOE

Later studies that cite this one

2 studies in the alzhub library list this one in their references.

• Inhibitors of cathepsin B improve memory and reduce beta-amyloid in transgenic Alzheimer disease mice expressing the wild-type, but not the Swedish mutant, beta-secretase site of the amyloid precursor protein The Journal of biological chemistry · 2008-01-09 · usefulness score 44/100 · Risk genes beyond APOE
• MicroRNA-193b is a regulator of amyloid precursor protein in the blood and cerebrospinal fluid derived exosomal microRNA-193b is a biomarker of Alzheimer's disease Molecular medicine reports · 2014-08-12 · usefulness score 40/100 · Genetics

Related studies in Genetics

• Modulation of Alzheimer-like synaptic and cholinergic deficits in transgenic mice by human apolipoprotein E depends on isoform, aging, and overexpression of amyloid beta peptides but not on plaque formation The Journal of neuroscience : the official journal of the Society for Neuroscience · 2002-12-01 · usefulness score 48/100
• Lack of LDL receptor aggravates learning deficits and amyloid deposits in Alzheimer transgenic mice Neurobiology of aging · 2005-10-19 · usefulness score 43/100
• Genetic modification of the phenotypes produced by amyloid precursor protein overexpression in transgenic mice Human molecular genetics · 1997-10-01 · usefulness score 42/100
• Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease Experimental neurology · 2004-07-01 · usefulness score 42/100
• The evolution of A beta peptide burden in the APP23 transgenic mice: implications for A beta deposition in Alzheimer disease Molecular medicine (Cambridge, Mass.) · 2001-09-01 · usefulness score 40/100
• Increased amyloid- levels in APPSWE transgenic mice treated chronically with a physiological high-fat high-cholesterol diet The journal of nutrition, health & aging · 2002-01-01 · usefulness score 36/100

Also in Genetics

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• Associations of the Top 20 Alzheimer Disease Risk Variants With Brain Amyloidosis JAMA neurology · 2018-03-01 · usefulness score 55/100 · Genetics
• NOVEL DRUG DELIVERY SYSTEM: A PANDORA BOX FOR THE MANAGE MENT OF ALZHEIMER NOVEL DRUG DELIVERY IN ALZHEIMER Genetics and Molecular Research · 2026-06-02 · usefulness score 27/100 · Genetics
• Dissecting Alzheimer Disease Heritability Across Multiple Populations Alzheimer s & Dementia · 2025-12-01 · usefulness score 45/100 · Genetics

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