The leading cause of dementia is Alzheimer’s disease (AD), which affects millions worldwide. Aging populations
can foretell the worsening burden of the disease in the future. AD is characterised by the following hallmark
pathologies: amyloid-β over-production and deposition, abnormal hyperphosphorylation of tau leading to the
formation ...
The leading cause of dementia is Alzheimer’s disease (AD), which affects millions worldwide. Aging populations
can foretell the worsening burden of the disease in the future. AD is characterised by the following hallmark
pathologies: amyloid-β over-production and deposition, abnormal hyperphosphorylation of tau leading to the
formation of neurofibrillary tangles, and neuroinflammation. Many potential treatments fail in clinical trials,
suggesting that present theories are outdated or lead to therapeutic dead-ends. A gum disease-causing species
of bacteria, Porphyromonas gingivalis, is being increasingly linked with AD, given the ubiquity of gum disease
amongst older populations, and studies have revealed that the bacteria causes and exacerbates AD pathology
both in vitro and in vivo. P. gingivalis produce many neurotoxic molecules, including gingipain enzymes, lipopolysaccharide and phosphoglycerol dihydroceramides, and all of these have been shown to affect AD pathologies.
Numerous mechanisms by which these neurotoxic species reach the brain have been proposed, and one of these
is the bacteria’s use of outer membrane vesicles. This review presents the present evidence of the effects of P. gingivalis and its outer membrane vesicles, gingipains, lipopolysaccharide and phosphoglycerol dihydroceramides,
on neurodegeneration in neuronal cultures, mice models and post-mortem studies, and determines how this
evidence can be used to develop new treatments for AD.
