Stockholm. Chlamydia pneumoniae is an insidious intracellular bacterium to which almost the entire worldwide population has been exposed by age 70. It primarily causes inflammatory lung disease but has in the past decade been implicated in the development of atherosclerotic plaques. Yesterday at the 8th International Conference on Alzheimer’s Disease and Related Disorders, Brian Balin and colleagues at the Philadelphia College of Osteopathic Medicine presented data showing that chlamydia isolated from Alzheimer’s brain, cultured, and then sprayed into the noses of young wild-type BALB/c mice can cause progressive deposition of amyloid plaques, in essence creating a partial model of AD without using any transgenes. At 15 months, plaque load rises steeply, Balin said.
“We believe this could be a trigger mechanism for the pathology in AD,” said Balin. “People have been suspecting this for decades but could not find anything. It is very difficult to pinpoint an infectious cause for a progressive, chronic disease. We also believe that our isolation of chlamydia from the human AD brain and induction of pathology in normal mice is proof of principle that this can be a causative mechanism turning on pathology.”
Balin and colleagues identified the plaques with Aβ42 antibodies and thioflavin-S staining. They have not found neurofibrillary tangles in their mice, but are currently looking for tau accumulation and neuritic dystrophy in older animals. They also have not yet looked for behavioral deficits.
Interestingly, Balin and his colleagues found the bacterium primarily in microglia, astroglia, and perivascular macrophages, both in human and the mice. A poster on Wednesday examines pathways by which this organism can enter the brain after a respiratory tract infection, essentially suggesting that blood monocytes harboring the pathogen can penetrate the blood-brain barrier by altering tight junctions. Balin believes that chlamydia, which is known to upregulate the expression of proinflammatory cytokines, may induce amyloid pathology as a consequence of this glia-derived inflammation.
In 1998, these researchers reported in Medical Microbioloy and Immunology that of 50 brains of sporadic AD cases, 90 percent had chlamydia in their brains, whereas only five percent of the controls did. Since exposure is widespread, this begs the question which genetic host response factors may allow some people to shed the infection more effectively than others. These could be among genetic risk factors for some cases of sporadic AD, said Balin. For a start, Alan Hudson and colleagues at Wayne State University School of Medicine in Detroit, Michigan, tomorrow are presenting data suggesting that cultured human astrocytes are more easily infected with chlamydia if they are ApoE4 positive than if they carry the other ApoE alleles, and that ApoE4-positive samples of frontal and temporal cortex and hippocampus of AD brains had higher bacterial load than did samples carrying E2 or E3.—Gabrielle Strobel
No Available References
- Gérard HC, Wang GF, Balin BJ, Schumacher HR, Hudson AP. Frequency of apolipoprotein E (APOE) allele types in patients with Chlamydia-associated arthritis and other arthritides. Microb Pathog. 1999 Jan;26(1):35-43. PubMed.
- Balin BJ, Appelt DM. Role of infection in Alzheimer's disease. J Am Osteopath Assoc. 2001 Dec;101(12 Suppl Pt 1):S1-6. PubMed.
- Balin BJ, Gérard HC, Arking EJ, Appelt DM, Branigan PJ, Abrams JT, Whittum-Hudson JA, Hudson AP. Identification and localization of Chlamydia pneumoniae in the Alzheimer's brain. Med Microbiol Immunol. 1998 Jun;187(1):23-42. PubMed.