RAGE, LRP-1, and amyloid-beta protein in Alzheimer’s disease
Abstract
The receptor for advanced glycation end products (RAGE) is thought to be a primary transporter of beta-amyloid across the blood-brain barrier (BBB) into the brain from the systemic circulation, while the low-density lipoprotein receptor-related protein (LRP)-1 mediates transport of beta-amyloid out of the brain. To determine whether there are Alzheimer's disease (AD)-related changes in these BBB-associated beta-amyloid receptors, we studied RAGE, LRP-1, and beta-amyloid in human elderly control and AD hippocampi. In control hippocampi, there was robust RAGE immunoreactivity in neurons, whereas microvascular staining was barely detectable. LRP-1 staining, in contrast, was clearly evident within microvessels but only weakly stained neurons. In AD cases, neuronal RAGE immunoreactivity was significantly decreased. An unexpected finding was the strongly positive microvascular RAGE immunoreactivity. No evidence for colocalization of RAGE and beta-amyloid was seen within either microvessels or senile plaques. A reversed pattern was evident for LRP-1 in AD. There was very strong staining for LRP-1 in neurons, with minimal microvascular staining. Unlike RAGE, colocalization of LRP-1 and beta-amyloid was clearly present within senile plaques but not microvessels. Western blot analysis revealed a much higher concentration of RAGE protein in AD hippocampi as compared with controls. Concentration of LRP-1 was increased in AD hippocampi, likely secondary to its colocalization with senile p…
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LRP1 levels at the blood-brain barrier are diminished in Alzheimer's disease and Alzheimer's disease models, contributing to Aβ accumulation in the brain.
“LRP1 levels at the BBB are diminished in AD and AD models contributing to A 𝛃 accumulation in the brain (137, 152, 410, 535).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [152]
RAGE expression at the blood-brain barrier is increased in Alzheimer's disease and Alzheimer's disease models.
“Its expression at the BBB is increased in AD and AD models (134, 152, 410).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [152]
In Alzheimer's disease, brain microvessels exhibit reduced levels of LRP1, a major amyloid-beta clearance receptor at the blood-brain barrier.
“AD brain microvessels also exhibit reduced levels of LRP1, a major A 𝛃 clearance receptor at the BBB (137, 152, 230, 410, 535).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [152]
RAGE expression is increased in Alzheimer's disease brain endothelium and mural cells.
“In contrast to LRP1, expression of RAGE, a major A 𝛃 influx receptor, is increased in AD brain endothelium and mural cells (134, 152, 410)”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [152]
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References 32 · Cited by 519
- Authors
- Donahue, J. E., Flaherty, S. L., Johanson, C. E., Duncan, J. A., Silverberg, G. D., Miller, M. C., Tavares, R., Yang, W., Wu, Q., Sabo, E., Hovanesian, V., & Stopa, E. G.
- Affiliations
- Brown University (US)
- Stanford Medicine (US)
- Beth Israel Deaconess Medical Center (US)
- Rhode Island Hospital (US)
- Corresponding author
- Donahue, John E.
- Venue
- Acta Neuropathologica
- Published
- 2006-07-25
- Volume
- 112
- Issue
- 4
- Pages
- 405-415
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2091910339
- Cited by
- 519
- References
- 32
- Citations by year
- 2026: 18 · 2025: 35 · 2024: 23 · 2023: 23 · 2022: 31 · 2021: 41 · 2020: 28 · 2019: 29 · 2018: 27 · 2017: 18 · 2016: 15 · 2015: 33 · 2014: 25 · 2013: 21 · 2012: 31
- FWCI
- 13.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging
- National Institute of Mental Health (R24MH068855)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- Alzheimer's disease, receptor for advanced glycation end products, LRP1, low density lipoprotein receptor-related protein, amyloid-beta, blood-brain barrier, hippocampus, amyloid plaques, microvessels
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Humans, Immunohistochemistry, Male, Neurons, Blotting, Western, Amyloid beta-Peptides, Glycation End Products, Advanced, Low Density Lipoprotein Receptor-Related Protein-1
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