The open access paper noted here reports on the use of a genetic analysis to shed further light on the relative importance of shared mechanisms across a range of neurodegenerative conditions in which tau aggregation is thought to be important. The researchers find associations in gene expression between these conditions that suggesting microglial dysfunction is an important common determinant of disease progression.
If one looks over all of the most common neurodegenerative diseases, patients exhibit a number of overlapping mechanisms that appear plausible as proximate causes of brain cell dysfunction and death. Some conditions share the aggregation of damaged proteins such as amyloid-β and tau. Most share harmful alterations in the behavior of immune cells such as microglia, either causing or responding to a state of raised chronic inflammation. The progression of vascular aging, leading to inadequate delivery of oxygen and nutrients, and mitochondrial dysfunction are also common in neurodegenerative conditions. All of these observations, sadly, tell us far less than we’d like about cause and effect in the aging brain. All of the signs progress over time, and absent technologies that can carefully block one of those signs, in order to see what happens next, it is very
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