CBD: SOME ANSWERS( continued)
What are the various subtypes of CBD?
The microscopic brain abnormalities of CBD can affect different parts of the brain, producing different sets of outward symptoms in different people. The first variant to be described in the medical literature is called corticobasal syndrome and is the most common. It affects about half of all people with CBD and is the archetype of CBD described above.
About 25 % of people with CBD have an outward appearance that resembles the most common form of PSP, which features problems with balance, eye movement, speech, and swallowing. Another 15 % have frontotemporal dementia, with inappropriately uninhibited behavior and difficulty organizing thoughts. Then there are two rare forms, each accounting for about 5 % of the total. One has a dementia similar to that of Alzheimer’ s disease, with important problems with memory or spatial orientation. The other is a form of aphasia, a problem with language, in this case difficulty finding words and obeying rules of grammar.
All forms of CBD at some point include, in almost all patients, a degree of“ motor parkinsonism,” meaning stiffness, slowness, soft speech, and reduction in facial expression, sometimes with balance difficulty and tremor..
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Is CBD genetic?
CBD almost never runs in families. However, a variant in the gene on chromosome 17 that encodes the tau protein is a little more common in CBD than in the rest of the population. Called the“ H1 haplotype,” it occurs in 92 % of people with CBD and in 60-77 % of the rest of the population. So the H1 haplotype is( nearly) necessary but far from sufficient to cause the disease.
We’ re still not quite sure how the H1 haplotype increases CBD risk. One possibility is that it simply increases the amount of tau produced, which causes that protein to stick together, even if it’ s not misfolded. Another possibility, discovered only this year, is that it causes too many“ methyl groups” to stick to the tau gene, which alters its function. A methyl group is simply a carbon atom with three hydrogens. It can be attached to large molecules including DNA. Methylation is a normal way for the cell to regulate the function of DNA, thereby affecting the function of genes without actually changing the content of the genetic code like ordinary mutations do. This is exciting because certain molecules have the potential to be developed into drugs that could alter DNA methylation.
A detailed analysis of the genetics of CBD was published in 2015 by an international group of researchers. The project was partly sponsored by CurePSP. It found five genetic variants to be associated with CBD in addition to the H1 haplotype in the gene for tau. One of these genes, called MOBP, is also associated with PSP. It is the blueprint for the manufacture of a protein in brain cells’ myelin sheath, which serves as a layer of electrical insulation on the wires connecting brain cells together. These findings await confirmation by other research groups using other methods.
If these gene variants are confirmed, the next step will be to figure out how those errors damage the normal function of brain cells. Those insights, in turn, will provide new ideas for drug targets. In other words, once scientists work out which steps in the brain cells’ normal function become disordered as a result of these CBD-related gene variations, they will know where new drugs could be directed to prevent the process from proceeding further. Coupled with a test to detect CBD in its earliest stages, before it actually causes any disability, such a drug treatment would amount to a CBD prevention.