RESEARCH NEWS: Infectious link to Alzheimer's disease

[Guest guest]

This seems to be pretty big news concerning a possible cause of Alzheimer's.

Regards,

Pam

------------------

http://news.bmn.com/news/story?day=021031 & story=2

Infectious link to Alzheimer's disease

30 October 2002 17:00 EST

by a Habeck

Infecting normal mice intranasally with the respiratory pathogen Chlamydia

pneumoniae promotes plaque development consistent with Alzheimer's disease,

US researchers will report next month at the Society for Neuroscience

meeting in Orlando. The finding provides the Alzheimer's world with a

long-needed experimental model for sporadic, late-onset Alzheimer's disease

(AD) - and, possibly, with a culprit for the disease.

Human AD can be attributed to a genetic defect in only 5% of cases. " The

question in my mind has always been: How do you take a disease that is this

prevalent and explain its presence in a genetically heterogeneous population

such as human beings? " said Karl Herrup, professor of neurosciences at Case

Western Reserve University.

Infection with C. pneumoniae is a possible answer. A cousin of the more

widely known sexually-transmitted C. trachomatis, C. pneumoniae is a common

respiratory pathogen that causes acute and chronic conditions such as

pneumonia, sinusitis and chronic obstructive pulmonary disease. A small

bacterium, it can survive inside host cells for years and cause inflammatory

responses.

C. pneumoniae made the news in the early 1990s, when it was found living in

atherosclerotic plaques. Since then, C. pneumoniae infection has been

implicated in the development of atherosclerosis. Curious to see whether it

can also infect the nervous system, Balin, Denah Appelt (now at

Philadelphia College of Osteopathic Medicine), and Alan Hudson of Wayne

State University analyzed post-mortem brains of 38 AD patients and controls.

A majority of AD patients had the bacterium in brain regions affected by the

disease, while only one control was PCR-positive. The researchers even

succeeded in culturing the bacterium isolated from AD brains.

A few negative reports followed, but chlamydiologist Mahony of

McMaster University believes these were due to sampling errors, because

cutting serial sections within a paraffin block is " hit and miss. " There is

" no question in my mind that [chlamydia] is in the brain, " says Mahony, who

has corroborated Balin's findings. But the question remains whether it plays

a causal role in AD.

Four years on, Balin and Appelt presented new data that caught the attention

of virtually every delegate at the International Alzheimer's meeting in

Sweden in July this year. Little, a post-doc in Appelt's and Balin's

lab, had infected non-transgenic BALB/c mice with a strain of C. pneumoniae

isolated from an AD patient or vehicle alone.

Within 1-3 months, the researchers found plaques immunoreactive for A-beta

1-42 in the mouse brains. According to Appelt, the plaque load in infected

animals rose over time and did not clear a year after infection. Control

animals did not develop comparable plaques.

Herrup, who attended the meeting in Sweden, said the study was " well done "

and " rigorously analyzed, " which demanded that Alzheimer's researchers take

serious note.

For a start, someone else must confirm the results. Meanwhile, Balin and

Appelt have already done their own control experiments, and have infected

BALB/c mice with a respiratory strain of C. pneumoniae. Preliminary evidence

indicates this strain also promotes plaque development in the BALB/c brain,

they will report at the Society for Neuroscience meeting in Orlando this

month.

The jury is still out as to whether the infected mice also develop the

second pathogenic hallmark of AD, neurofibrillary tangles. Appelt and Balin

are investigating this, and are also gearing up to do some behavioral

studies.

" I think the most stunning implication is that the mouse nervous system is

capable of producing Alzheimer-like plaques without the use of genetic

trickery, " said Herrup. Having a non-genetic model of AD would enhance the

field and " make our drug- and therapy-testing much more apprehensive. "

Mahony agrees: " It will be very interesting to play with the model and see

if you can block the formation of plaques by intervening at some point in

whatever pathway of events you think occurs. " He suggests blocking the

action of cytokines, to see whether chlamydia contributes to inflammation

that may play a key role in AD.

Balin and Appelt have already found another clue to chlamydia's role in AD.

Having infected cultured monocytes and endothelial cells with C. pneumoniae,

they observed that it actually upregulates the production and processing of

the amyloid protein. " We think that there is a direct effect of the organism

on amyloid, and that is how we think it will play into the Alzheimer

problem, " Balin said.

Time and more research will tell whether and how C. pneumoniae is involved

the development of AD. " My prediction would be that we are not looking at

the cause of all AD, " said Herrup, " but that we might actually be getting

insight into the kinds of insults that lead to the development of the

sporadic form. We already think that vascular factors predispose. To have

another route to disease can only help the field. "

Balin now wants to set up clinical trials testing the effect of antibiotics

used against C. pneumoniae in patients with late-onset AD. " Right now, we

are thinking that combining antibiotics and anti-inflammatory drugs might be

instrumental in treating AD, " he added. Antibiotics alone might offer hope

to people with sporadic AD who show signs of chlamydia infections, he says,

but it remains uncertain whether antibiotics can ever eradicate the organism

permanently.

[Guest guest]

This seems to be pretty big news concerning a possible cause of Alzheimer's.

Regards,

Pam

------------------

http://news.bmn.com/news/story?day=021031 & story=2

Infectious link to Alzheimer's disease

30 October 2002 17:00 EST

by a Habeck

Infecting normal mice intranasally with the respiratory pathogen Chlamydia

pneumoniae promotes plaque development consistent with Alzheimer's disease,

US researchers will report next month at the Society for Neuroscience

meeting in Orlando. The finding provides the Alzheimer's world with a

long-needed experimental model for sporadic, late-onset Alzheimer's disease

(AD) - and, possibly, with a culprit for the disease.

Human AD can be attributed to a genetic defect in only 5% of cases. " The

question in my mind has always been: How do you take a disease that is this

prevalent and explain its presence in a genetically heterogeneous population

such as human beings? " said Karl Herrup, professor of neurosciences at Case

Western Reserve University.

Infection with C. pneumoniae is a possible answer. A cousin of the more

widely known sexually-transmitted C. trachomatis, C. pneumoniae is a common

respiratory pathogen that causes acute and chronic conditions such as

pneumonia, sinusitis and chronic obstructive pulmonary disease. A small

bacterium, it can survive inside host cells for years and cause inflammatory

responses.

C. pneumoniae made the news in the early 1990s, when it was found living in

atherosclerotic plaques. Since then, C. pneumoniae infection has been

implicated in the development of atherosclerosis. Curious to see whether it

can also infect the nervous system, Balin, Denah Appelt (now at

Philadelphia College of Osteopathic Medicine), and Alan Hudson of Wayne

State University analyzed post-mortem brains of 38 AD patients and controls.

A majority of AD patients had the bacterium in brain regions affected by the

disease, while only one control was PCR-positive. The researchers even

succeeded in culturing the bacterium isolated from AD brains.

A few negative reports followed, but chlamydiologist Mahony of

McMaster University believes these were due to sampling errors, because

cutting serial sections within a paraffin block is " hit and miss. " There is

" no question in my mind that [chlamydia] is in the brain, " says Mahony, who

has corroborated Balin's findings. But the question remains whether it plays

a causal role in AD.

Four years on, Balin and Appelt presented new data that caught the attention

of virtually every delegate at the International Alzheimer's meeting in

Sweden in July this year. Little, a post-doc in Appelt's and Balin's

lab, had infected non-transgenic BALB/c mice with a strain of C. pneumoniae

isolated from an AD patient or vehicle alone.

Within 1-3 months, the researchers found plaques immunoreactive for A-beta

1-42 in the mouse brains. According to Appelt, the plaque load in infected

animals rose over time and did not clear a year after infection. Control

animals did not develop comparable plaques.

Herrup, who attended the meeting in Sweden, said the study was " well done "

and " rigorously analyzed, " which demanded that Alzheimer's researchers take

serious note.

For a start, someone else must confirm the results. Meanwhile, Balin and

Appelt have already done their own control experiments, and have infected

BALB/c mice with a respiratory strain of C. pneumoniae. Preliminary evidence

indicates this strain also promotes plaque development in the BALB/c brain,

they will report at the Society for Neuroscience meeting in Orlando this

month.

The jury is still out as to whether the infected mice also develop the

second pathogenic hallmark of AD, neurofibrillary tangles. Appelt and Balin

are investigating this, and are also gearing up to do some behavioral

studies.

" I think the most stunning implication is that the mouse nervous system is

capable of producing Alzheimer-like plaques without the use of genetic

trickery, " said Herrup. Having a non-genetic model of AD would enhance the

field and " make our drug- and therapy-testing much more apprehensive. "

Mahony agrees: " It will be very interesting to play with the model and see

if you can block the formation of plaques by intervening at some point in

whatever pathway of events you think occurs. " He suggests blocking the

action of cytokines, to see whether chlamydia contributes to inflammation

that may play a key role in AD.

Balin and Appelt have already found another clue to chlamydia's role in AD.

Having infected cultured monocytes and endothelial cells with C. pneumoniae,

they observed that it actually upregulates the production and processing of

the amyloid protein. " We think that there is a direct effect of the organism

on amyloid, and that is how we think it will play into the Alzheimer

problem, " Balin said.

Time and more research will tell whether and how C. pneumoniae is involved

the development of AD. " My prediction would be that we are not looking at

the cause of all AD, " said Herrup, " but that we might actually be getting

insight into the kinds of insults that lead to the development of the

sporadic form. We already think that vascular factors predispose. To have

another route to disease can only help the field. "

Balin now wants to set up clinical trials testing the effect of antibiotics

used against C. pneumoniae in patients with late-onset AD. " Right now, we

are thinking that combining antibiotics and anti-inflammatory drugs might be

instrumental in treating AD, " he added. Antibiotics alone might offer hope

to people with sporadic AD who show signs of chlamydia infections, he says,

but it remains uncertain whether antibiotics can ever eradicate the organism

permanently.