Alzheimers - Autism herpes connection?

[Guest guest]

From

http://www.livescience.com/humanbiology/070103_herpes_alzheimers.html

Herpes Might Cause Alzheimer's

By Robin Lloyd

Senior Editor

posted: 03 January 2007

New research supports growing concerns that herpes plays a role in

the development of Alzheimer's disease, the most common form of

dementia.

The latest work, announced today, shows a link between a gene and

herpes simplex 1, or HSV. The form of the ApoE gene called ApoE-4 is

the leading known risk factor for Alzheimer's. And HSV is the form

of herpes that causes cold sores around the mouth. More than 80

percent of Americans are infected with HSV.

The researchers, at the University of Rochester Medical Center,

found that ApoE-4 effectively puts out a welcome mat for the herpes

virus, allowing it to be more active in the brain.

" The data suggest that ApoE-4 may support the ability of HSV to be a

more virulent pathogen, " said Federoff, lead author of the

research published online in the journal Neurobiology of Aging.

The research involved measuring the activity levels of HSV in the

brains of mice with different forms of the human ApoE gene.

The team found that the virus infiltrates brain cells about the same

whether or not mice have the ApoE-4 form of the gene. But in mice

with the ApoE-4 version, the virus is less likely to be latent and

thus more likely to multiply.

Scientists have known for several years that the ApoE-4 gene plays a

role in Alzheimer's but the idea that it works in concert with the

herpes virus is new.

Ruth Itzhaki of the University of Manchester has conducted several

studies showing a correlation between herpes and Alzheimer's.

Patients suffering from the dementia disease who also have the ApoE-

4 form of the gene also have more herpes DNA in the brain regions

that are affected by Alzheimer's, she found. And people with the

ApoE-4 version of the gene who have HSV are more likely to get

Alzheimer's than those who lack either the gene version and the

virus.

Also, other scientists have found that people who frequently break

out in cold sores are more likely to have the gene that makes them

more vulnerable to Alzheimer's.

HSV is a chronic infection that lives in people for a lifetime,

periodically flaring up. The virus is usually latent, locked inside

cells, but occasionally stress, fatigue, certain foods and even

sunlight can spark the virus into an active phase that damages cells

and causes cold sores.

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I also found a full-text free article from the journal, Herpes, at

http://www.ihmf.org/journal/download/11Itzhaki(77A)sup277A.pdf

Herpes Simplex Virus Type Apolipoprotein E and Alzheimer's Disease

Ruth Itzhaki, Molecular Neurobiology Laboratory, Department of

Optometry and Neuroscience,

University of Manchester Institute of Science and Technology,

Manchester, UK.

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Here are a few abstracts of ApoE-4 and autism related articles.

1.

Psychiatr Genet. 2004 Jun;14(2):73-82.

Enhanced APOE2 transmission rates in families with autistic

probands.

Persico AM, D'Agruma L, Zelante L, Militerni R, Bravaccio C,

Schneider C, Melmed R, Trillo S, Montecchi F, Elia M, Palermo M,

Rabinowitz D, Pascucci T, Puglisi-Allegra S, Reichelt KL, Muscarella

L, Guarnieri V, Melgari JM, Conciatori M, Keller F.

Laboratory of Molecular Psychiatry and Neurogenetics,

University 'Campus Bio-Medico', Rome, Italy. a.persico@...

We have previously described linkage/association between reelin gene

polymorphisms and autistic disorder. APOE also participates in the

Reelin signaling pathway, by competitively antagonizing Reelin

binding to APOE receptor 2 and to very-low-density lipoprotein

receptors. The APOE2 protein variant displays the lowest receptor

binding affinity compared with APOE3 and APOE4. In this study, we

assess linkage/association between primary autism and APOE alleles

in 223 complete trios, from 119 simplex Italian families and 44

simplex and 29 multiplex Caucasian-American families. Statistically

significant disequilibrium favors the transmission of epsilon2

alleles to autistic offspring, over epsilon3 and epsilon4 (allele-

wise transmission/disequilibrium test [TDT], chi2 = 6.16, 2 degrees

of freedom [d.f.], P<0.05; genotype-wise TDT, chi2 = 10.68, 3 d.f.,

P<0.05). A novel epsilon3r allele was also discovered in an autistic

child and his mother. Autistic patients do not differ significantly

from unaffected siblings (allele-wise TDT comparing autistic

patients versus unaffected sibs, chi2 = 1.83, 2 d.f., P<0.40, not

significant). The major limitation of this study consists of our

small sample size of trios including one unaffected sibling,

currently not possessing the statistical power necessary to

conclusively discriminate a specific association of epsilon2 with

autism, from a distorted segregation pattern characterized by

enhanced epsilon2 transmission rates both to affected and unaffected

offspring. Our findings are thus compatible with either (a)

pathogenetic contributions by epsilon2 alleles to autism spectrum

vulnerability, requiring additional environmental and/or genetic

factors to yield an autistic syndrome, and/or ( a protective

effect of epsilon2 alleles against the enhanced risk of miscarriage

and infertility previously described among parents of autistic

children.

2.

Am J Med Genet B Neuropsychiatr Genet. 2004 Feb 15;125(1):57-60.

No association between the APOE gene and autism.

Raiford KL, Shao Y, IC, ER, Menold MM, HH,

Abramson RK, Worley G, DeLong GR, Vance JM, Cuccaro ML, Gilbert JR,

Pericak-Vance MA.

Department of Medicine and Center for Human Genetics, Duke

University Medical Center, Durham, North Carolina 27710, USA.

Autism is a neurodevelopmental disorder characterized by stereotypic

and repetitive behavior and interests, together with social and

communicative deficiencies. The results of several genomic screens

suggest the presence of an autism susceptibility locus on chromosome

19p13.2-q13.4. The apolipoprotein E (APOE) gene on chromosome 19

encodes for a protein, apoE, whose different isoforms (E2, E3, E4)

influence neuronal growth. APOE participates in lipid transport and

metabolism, repair, growth, and maintenance of axons and myelin

during neuronal development. The APOE protein competes with the

Reelin protein for VLDL/APOER2 receptor binding. Several studies

have reported evidence for an association between autism and the

Reelin gene. Based on these data we tested for association between

APOE and autism using family-based association methods in a data set

of 322 autism families. Three promoter, one intronic, and one 3' UTR

single nucleotide polymorphisms (SNPs) in the APOE gene (-491a/t, -

427c/t, -219g/t, 113c/g, and 5361c/t) as well as the APOE functional

polymorphism (E2, E3, E4) were examined and failed to reveal

significant evidence that autism is associated with APOE.

3.

Neurobiol Learn Mem. 2006 Jan;85(1):16-29. Epub 2005 Sep 29.

A fresh look at an ancient receptor family: emerging roles for low

density lipoprotein receptors in synaptic plasticity and memory

formation.

Qiu S, Korwek KM, Weeber EJ.

Department of Molecular Physiology and Biophysics, Vanderbilt

University Medical Center, Nashville, TN 37232-0615, USA.

The well-known family of low-density lipoprotein receptors

represents a collection of ancient membrane receptors that have been

remarkably conserved throughout evolution. These multifunctional

receptors, known to regulate cholesterol transport, are becoming

increasingly interesting to the neuroscience community due to their

ability to transduce a diversity of extracellular signals across the

membrane in the adult CNS. Their roles in modulating synaptic

plasticity and necessity in hippocampus-specific learning and memory

have recently come to light. In addition, genetic, biochemical and

behavioral studies have implicated these signaling systems in a

number of human neurodegenerative and neuropsychiatric disorders

involving loss of cognitive ability, such as Alzheimer's disease,

schizophrenia and autism. This review describes the known functions

of these receptors and discusses their potential role in processes

of synaptic regulation and memory formation.

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Anybody have their child tested for the ApoE-4 allele?

Vance