Common mechanisms involved in Alzheimer's disease and type 2 diabetes: a key role of chronic bacterial infection and inflammation

Judith Miklossy, Patrick L McGeer, Judith Miklossy, Patrick L McGeer

Abstract

Strong epidemiologic evidence and common molecular mechanisms support an association between Alzheimer's disease (AD) and type 2-diabetes. Local inflammation and amyloidosis occur in both diseases and are associated with periodontitis and various infectious agents. This article reviews the evidence for the presence of local inflammation and bacteria in type 2 diabetes and discusses host pathogen interactions in chronic inflammatory disorders. Chlamydophyla pneumoniae, Helicobacter pylori and spirochetes are demonstrated in association with dementia and brain lesions in AD and islet lesions in type 2 diabetes. The presence of pathogens in host tissues activates immune responses through Toll-like receptor signaling pathways. Evasion of pathogens from complement-mediated attack results in persistent infection, inflammation and amyloidosis. Amyloid beta and the pancreatic amyloid called amylin bind to lipid bilayers and produce Ca(2+) influx and bacteriolysis. Similarly to AD, accumulation of amylin deposits in type 2 diabetes may result from an innate immune response to chronic bacterial infections, which are known to be associated with amyloidosis. Further research based on an infectious origin of both AD and type 2 diabetes may lead to novel treatment strategies.

Keywords: Alzheimer's disease; Chlamydia pneumoniae; Diabetes type 2; Helicobacter pylori; amyloid; infection; inflammation; spirochetes.

Conflict of interest statement

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1. LTR signaling in host defenses…
Figure 1. LTR signaling in host defenses against pathogens
Conserved components unique to microorganisms, like bacterial lipopolysaccharide (LPS), bacterial peptidoglycan (PGN) and bacterial lipoproteins (BLP), are called pathogen-associated molecular patterns (PAMPs). PAMPs are sensed by pattern recognition receptors (PRRs), which include CD14 and various Toll-like receptors (TLRs). LPS is recognized following its binding to lipoprotein binding protein (LBP). CD14, is part of the LPS receptor complex, and together with the functionally linked TLR2 and TLR4, and the associated molecule MD-2 (lymphocyte antigen 96) are expressed in the endocrine cells of human pancreatic islets. PRRs and TLRs signaling pathways play a major role in maintaining pathogen-free host tissues. When TLRs are activated by PAMPs, through NFκB signaling the innate and adaptive immune systems are activated. Invading bacteria are killed by the terminal attack complex (MAC) of the classical complement pathway and by specific anti-bacterial antibodies provided by the adaptive immune system.
Figure 2. Evasion of bacteria from destruction…
Figure 2. Evasion of bacteria from destruction by the host immune systems
Bacteria by suppressing, subverting or escaping host defenses will survive, proliferate and cause persistent chronic infection, sustained inflammation and slowly progressive host cell destruction.

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