Porphyromonas Gingivalis And Alzheimer’s Disease

Gum disease affects about ⅓ of all people, a drug that blocks the main toxins of P. gingivalis is entering clinical trials this year recent research shoes it may stop and even reverse Alzheimer’s disease and possibly give rise to a vaccine.

AD is a medical mystery, as populations age and grow so does dementia, which is now the 5th biggest cause of death around the globe, of which AD constitutes to some 70% of these deaths, yet what causes it is not fully understood.

Growing evidence suggests the function of amyloid proteins may be a defence against bacteria, inspiring recent studies looking at bacteria in AD, particularly those that cause gum disease which is a known risk for the condition, as bacteria involved in gum disease and other illness have been found after death in brain of those with disease. However it has not been clear whether these bacteria cause the disease or got in via brain damage cause by the condition until now.

Porphyromonas Gingivalis has been found to invade and inflame brain regions affected by AD; gum infections worsen symptoms in AD model mice; and it causes AD-like brain inflammation, neuronal damage, and amyloid plaques in healthy mice.

Cortexyme is reporting finding gingipain toxic enzymes used by Porphyromonas Gingivalis to feed on human tissue in 96% of the 54 AD brain samples they examined, and found the bacteria in all 3 Alzheimer’s brains whose DNA was examined, in the first report to show Porphyromonas Gingivalis DNA in human brains and the associated gingipains co-localising with plaques; gingipains were also shown to slice up tau proteins in ways that allow it to kill neurons.

Those who had experienced worse cognitive decline were found to have had the bacteria and its enzymes in higher levels. The bacteria was also found in the spinal fluid of those living with the disease, suggesting that the technique may provide a method of diagnosis.

When Porphyromonas Gingivalis was given to mice it lead to brain infection, amyloid production, tau tangles, and neural damage in regions and nerves typically affected by AD. Giving previously developed molecules that block gingipains to these mice was observed to reduce infections, halt amyloid production, lower brain inflammation, and rescue damaged neurons without developing resistance; antibiotics that kill Porphyromonas Gingivalis also did this but less effectively, and the bacteria developed rapid resistance.

Some brain samples from individuals without AD also had lower levels of Porphyromonas Gingivalis and protein accumulations. Amyloid and tau proteins can accumulate in the brain for 10-20 years before symptoms begin. According to the researchers Porphyromonas Gingivalis may be a cause for Alzheimer’s disease. Gum disease is more common, but AD strikes those who accumulate gingipains and damage the brain quickly enough to develop symptoms in their lifetime, which is believed to be a universal hypothesis of pathogenesis.

Cortexyme report their COR388 gingipain blockers have entered the brain, have passed initial safety tests in humans, and seemed to improve those with AD. Larger trials will launched looking for Porphyromonas Gingivalis in spinal fluid and cognitive improvements, both before and after. The company also plans to test against gum disease, and have a team in Melbourne working on developing a vaccine for Porphyromonas Gingivalis.