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Amyloid deposition and influx transporter expression at the blood-brain barrier increase in normal aging.
- Source :
-
Journal of neuropathology and experimental neurology [J Neuropathol Exp Neurol] 2010 Jan; Vol. 69 (1), pp. 98-108. - Publication Year :
- 2010
-
Abstract
- Aging is the most important single risk factor for developing Alzheimer disease. We measured amyloid-beta peptide (Abeta) levels in rat cerebral cortex and hippocampus during normal aging of Brown-Norway/Fischer rats. Amyloid-beta accumulation was associated with expression of the Abeta influx transporter, the receptor for advanced glycation end-products (RAGEs) at the blood-brain barrier. Rats at selected ages from 3 to 36 months were analyzed by 1) immunohistochemistry for amyloid deposition and quantitative microvessel surface area RAGE expression, 2) ELISA for cortical Abeta40 and Abeta42 concentrations, and 3) Western blotting of microvessel proteins for RAGE expression. Immunohistochemistry showed increasing accumulation of brain Abeta with aging. By ELISA analysis, both Abeta40 and Abeta42 concentrations in cortical homogenates rose sharply from 9 to 12 months. The Abeta42 continued to rise up to age 30 months, whereas Abeta40 stabilized after 12 months. The expression of RAGE initially decreased between 3 and 12 months but then increased between 12 and 34 months by immunohistochemistry. On immunoblotting, RAGE decreased up to 9 months and then progressively increased up to 36 months. These data indicate an association between amyloid and microvessel RAGE during aging. An increase in capillary RAGE expression seems to play a role in the later Abeta accumulation but not in the initial increase.
- Subjects :
- Age Factors
Animals
Brain metabolism
Enzyme-Linked Immunosorbent Assay methods
Male
Nerve Tissue Proteins metabolism
Peptide Fragments metabolism
Rats
Rats, Inbred F344
Receptor for Advanced Glycation End Products
Receptors, Immunologic genetics
Aging physiology
Amyloid metabolism
Amyloid beta-Peptides metabolism
Blood-Brain Barrier metabolism
Gene Expression Regulation physiology
Receptors, Immunologic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1554-6578
- Volume :
- 69
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of neuropathology and experimental neurology
- Publication Type :
- Academic Journal
- Accession number :
- 20010299
- Full Text :
- https://doi.org/10.1097/NEN.0b013e3181c8ad2f