Paper
- Alzforum Recommends
Montagne A, Barnes SR, Sweeney MD, Halliday MR, Sagare AP, Zhao Z, Toga AW, Jacobs RE, Liu CY, Amezcua L, Harrington MG, Chui HC, Law M, Zlokovic BV. Blood-brain barrier breakdown in the aging human hippocampus. Neuron. 2015 Jan 21;85(2):296-302. PubMed.
Recommends
Please login to recommend the paper.
Comments
St. Michael's Neurology and Pain Medicine
This is a very interesting concept. Almost three decades ago, we postulated the same hypothesis, based on histologic analysis of aged brains, demonstrating a blood brain barrier (BBB) breakdown and leakage of serum proteins in aged (but not young) human brain (Pappolla and Andorn, 1987). We also presented a potential mechanism as to how such BBB failure may contribute to age related neurodegeneration (Andorn et al., 1986; Andorn and Pappolla, 1989).
References:
Pappolla MA, Andorn AC. Serum protein leakage in aged human brain and inhibition of ligand binding at alpha 2-adrenergic and cholinergic binding sites. Synapse. 1987;1(1):82-9. PubMed.
Andorn AC, Pappolla MA, Fox H, Klemens FK, Martello PA. Human serum Cohn fraction IV (alpha-globulin [correction of globin] enriched) inhibits ligand binding at neurotransmitter receptors in human brain. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4572-5. PubMed.
Andorn AC, Pappolla MA. Serum protein interactions with neurotransmitter receptors: implications for Alzheimer's disease. Prog Clin Biol Res. 1989;317:695-701. PubMed.
View all comments by Mike Miguel PappollaSt. Michael's Neurology and Pain Medicine
This is a very interesting concept. Almost three decades ago, we postulated the same hypothesis, based on histologic analysis of aged brains, demonstrating a blood brain barrier (BBB) breakdown and leakage of serum proteins in aged (but not young) human brain (Pappolla and Andorn, 1987). We also presented a potential mechanism as to how such BBB failure may contribute to age related neurodegeneration (Andorn et al., 1986; Andorn and Pappolla, 1989).
References:
Pappolla MA, Andorn AC. Serum protein leakage in aged human brain and inhibition of ligand binding at alpha 2-adrenergic and cholinergic binding sites. Synapse. 1987;1(1):82-9. PubMed.
Andorn AC, Pappolla MA, Fox H, Klemens FK, Martello PA. Human serum Cohn fraction IV (alpha-globulin [correction of globin] enriched) inhibits ligand binding at neurotransmitter receptors in human brain. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4572-5. PubMed.
Andorn AC, Pappolla MA. Serum protein interactions with neurotransmitter receptors: implications for Alzheimer's disease. Prog Clin Biol Res. 1989;317:695-701. PubMed.
University of Wisconsin
The reason for a leaky blood-brain barrier (BBB) with aging may well rest with how dysregulated the HPG axis becomes after menopause and during andropause. We have previously demonstrated that changes in the concentration of sex hormones (gonadotropins, sex steroids) promote the loss of selective permeability of the BBB (Wilson et al., 2009). The hippocampus is rich in luteinizing hormone receptors, which might explain why changes are first seen in this structure. Gonadotropins are well known to regulate the vasculature (during implantation of the blastocyst, for example).
References:
Wilson AC, Clemente L, Liu T, Bowen RL, Meethal SV, Atwood CS. Reproductive hormones regulate the selective permeability of the blood-brain barrier. Biochim Biophys Acta. 2008 Jun;1782(6):401-7. Epub 2008 Mar 14 PubMed.
View all comments by Craig AtwoodMake a Comment
To make a comment you must login or register.