The nature of neurodegenerative diseases

Why don’t the homeostatic mechanisms that allow us to be extremely well-functioning individuals – let’s say from the age of 6 or 7, when we go to school and really enter society, to the age of 70 or 80 – just last longer? Why is it intrinsically difficult to keep these things working? There’s a superficial answer to that, which is that it’s matter – and matter will at some point start to fall apart. But why can’t other matter compensate for existing matter? We don’t really know. We have some inkling about the types of damage that accumulate and maybe that this type of chemical damage is irreversible simply because of the nature of matter, because of the laws of physics.

The deep answer to why that is and what you can do about it remains highly enigmatic. It’s very difficult to know today. Are there specific interventions to slow this process down? Can we stop it? That’s a completely open question. The other open question is, how come some brains age better than others? Why are some brains long-lasting and others not so much? Maybe part of the answer comes from what we know about neurodegenerative diseases.

There are neurodegenerative diseases that are mostly sporadic; that is to say, as of today, they’re not inherited. They don’t come from your parents, you just develop them. We can’t look at your genome or other aspects of your life and your brain and say, oh, you’re definitely going to get this disease by that age. So, those sporadically occurring neurodegenerative diseases are the majority, and they’re very difficult to get conclusions from. It turns out that a very small percentage of these neurodegenerative diseases like Parkinson’s, Alzheimer’s and others are actually genetic and heritable, meaning that mutations in a very specific gene will cause them 100% certainty.

In Alzheimer’s disease, there’s no removal of these genes, but very specific changes in their sequence. Now, whether those changes affect brain development or not, we still don’t know. However, we do know there are extremely rare examples of genetic forms of Parkinson’s disease that have impacted very young children, 9 or 15 years of age, who have been diagnosed with Parkinson’s-like symptoms and the loss of the parts of the brain that we see in Parkinson’s patients. So, that clearly means that in those particular individuals, that mutation, combined with other circumstances, led to a degenerative disease even before adulthood.

We can imagine that the brain is born with some level of vulnerability, and that in the worst-case scenario, we would express this vulnerability during the developmental phase of the brain so that children would be born with different functioning brains – what is called neurodiversity. On one end of this diversity spectrum, we might have people that are born with conditions like autism or fragile X disease or other developmental neurological affections. Other types of issues might appear and put people on the neurodiversity spectrum later in life, what we would today call neuropsychiatric affectations, for instance schizophrenia, depression, bipolar disorder.

Yet, other conditions would only appear later in life, what we would call neurodegenerative diseases. However, the idea would be that the seed of the problem, the seed of what would put those brains on a different place on the neurodiversity spectrum, would have already been planted very, very early in development – because a small minority of all of those issues can be directly traced back to a single mutation in a single gene or even specific mutations in a small number of genes.