Alzheimer's disease might depend on enabling pathogens which do not necessarily cross the blood-brain barrier.

The development of Alzheimer's Disease (AD) might reflect, in its acquired aspects, a cooperative pathogenesis whereby infectious enablers which do not necessarily cross the blood-brain barrier augment the invasive properties of a less virulent organism, thus enabling it to infect the brain. An example interaction is described which involves Chlamydia species, Human papillomavirus (HPV), microbiota, and yeast, where yeast is a pathogen of low virulence which crosses the blood-brain barrier. The cooperative pathogenesis begins at the mucosal epithelium. Infection by Chlamydia, HPV, or dysbiosis of commensal bacteria disrupts the integrity of the mucosal epithelium, thereby allowing colonizing yeast to penetrate the epithelial barrier and enter into the bloodstream. Chlamydia and enabling commensals promote insulin resistance, which provides yeast with glucose and also sets the stage for accumulation of amyloid beta protein (ABP). Meanwhile, HPV-induced and hyperglycemia-induced immunological changes enable the spread of newly invasive yeast to the brain, where the release of inflammatory cytokines in response to yeast promotes production of ABP. Chlamydia also cross reacts with Candida species, which may stimulate further brain inflammation in response to Candida and may augment production of ABP thereby The yeast's less virulent origins, coupled with immune modulation by enablers, might explain why AD as a model of infectious encephalitis is always slow and insidious rather than occasionally febrile, accompanied by seizures, or marked by signs of meningeal inflammation.