A recent article in the New Scientist journal entitled
“We may finally know what causes
Alzheimer’s – and how to stop it” reviews an intriguing and fairly
compelling alternative hypothesis, that the presence of bacteria in the brain
coming from gum infections with the common gum bacterium, Porphyromonas gingivalis, represents the primary cause of the
dementia and the formation of plaques and tangles is a secondary event. The classic proof that
a microbe causes a specific pure
culture disease involves four postulates first proposed by Robert Koch
in 1884: The bacteria must be
present in every case of the disease. The bacteria must be isolated from the
host with the disease and grown in pure culture. And finally, the specific
disease must be reproduced when the bacterium is inoculated into a healthy susceptible
host. These postulates have
been confirmed in the case of the bacterial hypothesis for Alzheimers: It was
found that P. gingivalis invades and
inflames brain regions affected in Alzheimers; that gum infections can worsen
symptoms in mice genetically engineered to have Alzheimers and can cause
Alzheimers-like brain inflammation, neural damage and amyloid plaques in healthy
mice. P. gingivalis is known to secrete
two toxic enzymes called gingipains. These were found in 99% of 54 human
Alzheimers brain samples from the hippocampus (The region for memory), and
also in the cerebral cortex in three Alzheimers brains. Normal brains sometimes
had P. gingivalis and gingipains, but
at low levels.
Chronic periodontitis
shows a correlation with dementia. It is thought that P. gingivalis can invade
white blood cells and cells lining blood vessels and could invade the brain in
that way. Invasion might also occur by way of cranial nerves near the mouth. The
mechanism for P. gingivalis brain infections to cause dementia could be by triggering
the release of amyloid, or it may directly damage the brain, e.g. through
inflammation.
The bacterial hypothesis does not eliminate a role for genetics. I copy below from the New Scientist article: "The biggest genetic risk factor for Alzheimer’s is a variant of the gene that makes the ApoE immune protein. Last year, a team in Sweden found that the gingipains released by P. gingivalis break up the ApoE protein into fragments, cleaving it at the site of a particular amino acid within the protein, and that these fragments may harm nerves. The ApoE4 variant of this protein contains more of this amino acid, suggesting that the reason people who make this variant are at a higher risk of developing Alzheimer’s may be because harmful levels of ApoE protein fragments build up more quickly in their brains than in those of other people."
The bacterial hypothesis does not eliminate a role for genetics. I copy below from the New Scientist article: "The biggest genetic risk factor for Alzheimer’s is a variant of the gene that makes the ApoE immune protein. Last year, a team in Sweden found that the gingipains released by P. gingivalis break up the ApoE protein into fragments, cleaving it at the site of a particular amino acid within the protein, and that these fragments may harm nerves. The ApoE4 variant of this protein contains more of this amino acid, suggesting that the reason people who make this variant are at a higher risk of developing Alzheimer’s may be because harmful levels of ApoE protein fragments build up more quickly in their brains than in those of other people."
If this hypothesis
proves correct, it could rapidly lead to effective treatments, such as by preventing
gum disease, or blocking gingipains with specific drugs. Initial results in
mice studies were very promising.
-- Now please excuse me, I
must go brush my teeth.
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