Evidence for seeding of beta -amyloid by intracerebral infusion of Alzheimer brain extracts in beta -amyloid precursor protein-transgenic mice

Topic: Brain proteins, microglia and lab models

Many neurodegenerative diseases are associated with the abnormal sequestration of disease-specific proteins in the brain, but the events that initiate this process remain unclear. To determine whether the deposition of the beta-amyloid peptide (Abeta), a key pathological feature of Alzheimer's disease (AD), can be induced in vivo, we infused dilute supernatants of autopsy-derived neocortical homogenates from Alzheimer's patients unilaterally into the hippocampus and neocortex of 3-month-old beta-amyloid precursor protein (betaAPP)-transgenic mice. Up to 4 weeks after the infusion there was no Abeta-deposition in the brain; however, after 5 months, the AD-tissue-injected hemisphere of the transgenic mice had developed profuse Abeta-immunoreactive senile plaques and vascular deposits, some of which were birefringent with Congo Red.

Key findings

• To determine whether the deposition of the beta-amyloid peptide (Abeta), a key pathological feature of Alzheimer's disease (AD), can be induced in vivo, we infused dilute supernatants of autopsy-derived neocortical homogenates from Alzheimer's patients unilaterally into the hippocampus and neocortex of 3-month-old beta-amyloid precursor protein (betaAPP)-transgenic mice.
• Up to 4 weeks after the infusion there was no Abeta-deposition in the brain; however, after 5 months, the AD-tissue-injected hemisphere of the transgenic mice had developed profuse Abeta-immunoreactive senile plaques and vascular deposits, some of which were birefringent with Congo Red.
• There was limited deposition of diffuse Abeta also in the brains of betaAPP-transgenic mice infused with tissue from an age-matched, non-AD brain with mild beta-amyloidosis, but none in mice receiving extract from a young control case.
• Abeta deposits also were not found in either vehicle-injected or uninjected transgenic mice or in any nontransgenic mice.

Why it matters

In beta-amyloid precursor protein-transgenic mice, infusing brain extracts from Alzheimer's patients induced A beta deposition after five months. This is an animal study showing that A beta deposition can be seeded, but it does not establish a treatment, cure, or prevention for Alzheimer's disease in people.

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Study details

• Evidence strengthLow

Read the original

• DOI: 10.1523/jneurosci.20-10-03606.2000
• PubMed: 10804202
• Original source →
• Free full text: Journal of Neuroscience →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{kane2000-10804202,
  author  = {Kane, M. D. and Lipinski, W. J. and Callahan, M. J. and Bian, F. and Durham, R. A. and Schwarz, R. D. and Roher, A. E. and Walker, L. C.},
  title   = {{Evidence for seeding of beta -amyloid by intracerebral infusion of Alzheimer brain extracts in beta -amyloid precursor protein-transgenic mice}},
  journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
  year    = {2000},
  doi     = {10.1523/jneurosci.20-10-03606.2000},
  pmid    = {10804202},
  url     = {https://doi.org/10.1523/jneurosci.20-10-03606.2000}
}

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
• A stop-codon mutation in the BRI gene associated with familial British dementia Nature · 1999-06-01 · usefulness score 52/100 · Brain tissue and pathology
• Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform Neuron · 1999-11-01 · usefulness score 50/100 · Lewy body dementia

Later studies that cite this one

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• Rapidly progressive Alzheimer's disease features distinct structures of amyloid-β Brain : a journal of neurology · 2015-02-15 · usefulness score 62/100 · Genetics
• Transmission and spreading of tauopathy in transgenic mouse brain Nature cell biology · 2009-06-07 · usefulness score 58/100 · Lewy body dementia
• The seeds of neurodegeneration: prion-like spreading in ALS Cell · 2011-10-01 · usefulness score 53/100 · Brain tissue and pathology
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• Amyloid-Beta (Aβ) Plaques Promote Seeding and Spreading of Alpha-Synuclein and Tau in a Mouse Model of Lewy Body Disorders with Aβ Pathology Neuron · 2019-11-20 · usefulness score 50/100 · Caregiving
• Mechanisms of Pathogenic Tau and Aβ Protein Spreading in Alzheimer's Disease Frontiers in aging neuroscience · 2020-08-27 · usefulness score 48/100 · Risk genes beyond APOE

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