The open access paper I’ll point out today makes the case for raising the profile of mechanisms other than protein aggregation in neurodegenerative conditions. The authors focus on Alzheimer’s disease, characterized by the aggregation of amyloid and tau in the brain, but the argument works just as well for most other forms of age-related dementia. That Alzheimer’s disease is the result of multiple mechanisms, each of which contributes to pathology to a similar degree, is one of the better explanations for the ongoing failure of clinical trials that focus solely on amyloid clearance. One only has to look at the sizable fraction of Alzheimer’s patients who are also diagnosed with vascular dementia to suspect that something of this nature might be an issue. If there are, for example, five important and somewhat independent mechanisms driving a specific medical condition, then the positive outcomes that result from partially addressing just one of those mechanisms may well get lost in the noise.
This class of issue is in fact endemic in attempts to interfere in the pathology of age-related disease at points that are distant from the root causes. The root causes of aging are