The consensus position on the role of amyloid-β as a meaningful cause of Alzheimer's disease is under attack. Removal of amyloid-β from human brains has so far failed to reverse or even meaningfully slow the condition, though there are certainly scenarios under which amyloid-β aggregates can be both a contributing cause of Alzheimer's and a poor target for therapy. For example, amyloid-β aggregation might generate sufficient cellular senescence and inflammation in microglia for that pathology to become self-sustaining even when the amyloid-β is later removed. Alternatively, rising levels of amyloid-β might be a side-effect of persistent infections that generate both chronic inflammation and microglial dysfunction sufficient to advance the disease. That second hypothesis, that Alzheimer's is the result of microbial infection, is emerging as the primary challenger to the established amyloid cascade view of the condition.
The infectious theory of Alzheimer's disease (AD) was first proposed some 30 years ago. Since then, the idea has encountered considerable resistance in the research community. Until recently, it had been largely displaced in favor of approaches based on the amyloid hypothesis, the leading theory of Alzheimer's, which identifies plaques of amyloid beta and tangles of tau protein as underlying drivers of the disease. The research landscape for AD, however, may be changing. The repeated failures of amyloid-targeting drugs along with recent discoveries supporting a microbial link to AD have generated fresh interest in this unorthodox approach.
Even before the amyloid hypothesis came under attack as a potential blind alley, alternate theories of the disease had been proposed. Perhaps Alzheimer's is caused not by accumulations of inanimate protein but rather by microorganisms, the way so many infectious diseases are. Researchers have used large data sets in order to explore the prevalence of two common herpesviruses sometimes found in Alzheimer's brain tissue. The study demonstrated that three viral strains appeared in greater abundance in brain samples derived from Alzheimer's patients, compared with normal brains. The viruses also seem to be implicated in the AD-related genetic networks associated with classic Alzheimer's pathology, including cell death, accumulation of amyloid-β and production of neurofibrillary tangles.
The pathogen theory has met with some hostility. Researchers may have insufficient background in microbiology or may inaccurately associate infectious agents solely with acute rather than chronic afflictions, though a number of microbial infections can indeed linger in the body asymptomatically for decades. Perhaps the greatest resistance to the pathogen theory comes from proponents of the amyloid hypothesis, some of whom believe that it will diminish research into amyloid plaques and tau tangles. A microbial link with AD and the amyloid hypothesis may be complementary rather than exclusionary, however. It is still possible that deposition of amyloid instigates a process of neurological decline, followed by opportunistic infections, or that the reverse is the case, with amyloid deposits representing a defense response to infection, trapping invasive microbes in sticky concentrations of amyloid.