IJV dysfunction in Down Syndrome

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

IJV dysfunction in Down Syndrome

Postby Cece » Wed Nov 06, 2013 8:43 pm

https://www.lablife.org/g?a=pubs_ll_no_user&id=22400025
Alzheimer's disease and vascular deficiency: lessons from imaging studies and down syndrome.

Authors:
Reed-Cossairt A, Zhu X, Lee HG, Reed C, Perry G, Petersen RB

Associated Labs:
Zhu/Lee Lab (Case Western Reserve University)

Curr Gerontol Geriatr Res. 2012 . 2012():929734.

PMID: 22400025

Down syndrome (DS) individuals are at high risk for developing Alzheimer's disease (AD) and consequently provide a unique opportunity to examine the factors leading to the onset of AD. This paper focuses on the neglected vascular parallels between AD and DS that can readily be examined in DS. Several recent AD studies provide evidence that internal jugular vein (IJV) reflux may result in white matter lesions and a 30% decrease in cerebrospinal fluid (CSF) clearance of amyloid-β. At the same time, studies analyzing the synthesis of amyloid-β in DS showed greater than expected amounts of Aβ than would be predicted by the increase in gene dosage, perhaps due to slower clearance. These studies are discussed along with the possibility that the venous and CSF dysfunction found in AD patients may be present early in life in persons with DS, leaving them particularly vulnerable to early onset AD. Studying IJV function in DS provides an opportunity to understand the role of vascular function in the initiation of AD.

http://www.hindawi.com/journals/cggr/2012/929734/

The research hasn't been done yet. This article is making the case for research on the IJV to be done in people with Down Syndrome.
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Re: IJV dysfunction in Down Syndrome

Postby cheerleader » Thu Nov 07, 2013 7:21 am

oh, wow. Great find, Cece.
Interesting that it was done at Case Western--where Diaconu proposed his CCSVI doppler/ jugular vein autopsy studies as a student.
This lab specializes in Alzheimer's and Parkinson's, but they are looking at mechanistics, too.
Looks like the Zhu/Lee Lab needs to get an invite to ISNVD!

cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Re: IJV dysfunction in Down Syndrome

Postby Cece » Thu Nov 07, 2013 10:00 am

What I like is that CCSVI may have kicked off a broader inquiry into venous drainage and CSF drainage in a variety of diseases and in normal aging.
I also like Case Western's lab and especially the Fox/Diaconu autopsy research. It would be nice to see some follow-up done on that, if not by Fox then at another institution.
Chronic, yet mild, dysfunction of the IJV beginning early in life, along with resulting impairment in CSF clearance, would leave persons with DS particularly vulnerable to the buildup of Aβ in the brain, which may be exacerbated by the overproduction of AβPP due to increased gene dosage.

That's in Down Syndrome, but if people with MS also have chronic mild dysfunction of the IJV with resulting impairment of CSF drainage, would we also be vulnerable to the build-up of AB that can lead to Alzheimer's?

According to this, no, there was no association seen between MS and Alzheimer's:
MS cases older than 64 years experienced development of AD pathology in comparable incidence as seen in the course of normal aging.
http://www.unboundmedicine.com/medline/citation/17924575/Multiple_sclerosis_and_Alzheimer's_disease_
Maybe a larger sample size would have teased out an association.

CSF APP and Ab peptides are reduced in MS: http://msj.sagepub.com/content/19/5/543.short
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