6.7. BACTERIAL PEPTIDOGLYCAN IS COLOCALIZED WITH SENILE PLAQUES, TANGLES AND CURLY FIBERS
Bacterial peptidoglycan, a cell wall component of bacteria (including spirochetes), is colocalized with senile plaques and neurofibrillary tangles in Alzheimer's disease
Bacterial peptidoglycan, the cell wall component of virtually all Eubacteria, including spirochetes, which is a potent stimulator of inflammation and amyloidosis had been detected immunohistochemically in senile plaques and neurofibrillary tangles of 17 AD cases analyzed and was absent in 7 control cases. In senile plaques bacterial peptidoglycan was co-localized with Aβ (Miklossy et al., 1996. Miklossy, 1998).
Miklossy J, Darekar P, Gern L, Janzer RC, Bosman FT. Bacterial peptidoglycan in neuritic plaques in Alzheimer’s disease. Azheimer’s Research, 1996; 2: 95-100.
Glycosaminoglycans (GAGs), which occur in most organisms from bacteria to vertebrates, appear to be present in all amyloid deposits regardless of the protein involved. Their early appearance, and their likely interaction with specific proteins imply that they play an essential role in the pathogenesis of amyloidosis. It is not known whether the increased accumulation of GAGs in amyloid plaques in Alzheimer's disease (AD) may be due to a parallel response of the GAG metabolism to an amyloidogenic stimulus or is secondary to the primary deposition of amyloid proteins. Increased accumulation of glycosaminoglycans and secondary amyloidosis may be induced by chronic bacterial infection or experimentally, by bacterial cell wall components. Recently, it has been observed that senile plaques are the site of chronic inflammation. Furthermore, experimental evidence has been reported suggesting that cerebral -amyloidosis of AD can be transmitted to primates.
In the present report we studied whether bacterial peptidoglycan, a potent inflammatory and amyloidogenic factor, can be immunohistochemically detected in senile plaques in AD. Frozen cortical brain sections from neuropathologically confirmed 17 AD cases, including 3 familial AD, were investigated. We found bacterial peptidoglycan to be immuno-localized to senile plaques and on serial, consecutive sections to be co-localized with -amyloid. We did not find bacterial peptidoglycan in 7 control cases without AD type histological changes.
These findings suggest that amyloidosis and increased accumulation of GAGs in senile plaques may be secondary to a chronic inflammatory stimulus. Further biochemical identification of the bacterial and host derived GAGs may help to clarify the role of heparan sulfate and other GAGs in pathogenesis of AD.
Miklossy J. Chronic inflammation and amyloidogenesis in Alzheimer's disease: Putative role of bacterial peptidoglycan, a potent inflammatory and amyloidogenic factor. Alzheimer's Dis Rev. 1998;3:45-51.
Glycosaminoglycans (GAGs), which occur in most organisms from bacteria to vertebrates, appear to be present in all amyloid deposits, and may play an essential role in the pathogenesis of amyloidosis. It is well established that senile plaques are the sites of chronic inflammation, but the factor activating the complement remain unknown. Here, we analyzed whether the amyloidogenic bacterial peptidoglycan, a potent activator of complement and of the GAG metabolic system is present in senile plaques. Neuropathologically analyzed 54 autopsied
brains were investigated. The 54 cases consisted of 32 Alzheimer's disease (AD) cases with severe AD-type changes, 12 cases with low number of senile plaques and 10 cases without any AD-type changes. We have found that in the 32 AD cases with high number of plaques and in the 12 cases with low number of plaques, bacterial peptidoglycan was immunolocalized to senile plaques and on serial sections co-localized with betaamyloid protein.
Bacterial peptidoglycan has a variety of biological actions in mammals. It is an inflammatory cytokine inducer, activates complement of the classic pathway, affects vascular permeability, generates nitric oxide, induces proteoglycan synthesis and apoptosis, in addition is amyloidogenic. It is well established that all these processes are implicated in AD, suggesting that bacteria or bacterial debris may be one among probably several factors which may trigger the cascade of events leading to chronic inflammation and amyloid deposition in AD.