Classifying Diseases Based on Autopsy

The idea of subtypes was created because of the recognition that within each neurodegenerative disease there are many diseases. But the way we have tried to classify those subtypes is by defining them based on what we can see. For instance, in Parkinson’s, if you have a tremor, you fall into a tremor subtype, if you don’t have it, it’s a tremor-less subtype. We have come to think of them as different subtypes. In creating those subtypes, we have predicted they will align with specific pathological and biological elements. The evidence, however, robustly suggests that they do not.

If a diagnosis of Parkinson’s is made at the bedside, and that person is ultimately examined after death, they will typically be found to have protein aggregates called Lewy bodies in their brain. This is how we confirm that what we said was Parkinson’s, was in fact Parkinson’s because on autopsy we found Lewy bodies. If so, then the next question that should be asked is: of the people who have autopsy-confirmed Parkinson’s, how many have another disease of brain ageing, such as what we refer to as Alzheimer’s? While the likelihood of having a second disease as we age may be 15 – 20%, studies consistently show that when we look at autopsies of individuals confirmed to have Parkinson’s, 80% of them would also meet the diagnostic criteria for Alzheimer’s.

Does that mean that 8 out of 10 people with Parkinson’s also develop Alzheimer’s? Or could it be that some biological abnormalities, in certain individuals, yield the aggregation of different kinds of proteins, which we currently classify as Parkinson’s and Alzheimer’s? It is very unlikely that by chance so many people have two diseases that are presumably very different from each other. It is more likely that these people have one disease that expresses proteins that we define, by virtue of our century-old models, as two separate diseases.

The time has come for us to abandon our old disease labels and start doing the hard work necessary to identify what is really going wrong in each individual’s biology, as we age.

– Prof. Alberto Espay

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