IPM Magazine

Volume 11, Issue No. 2, April 2024

It’s often asked why it has taken the best part of twenty years to get a new drug approved for Alzheimer’s. Well, the simple answer is research in neurobiology is complex. Alzheimer’s is a multifactorial disorder with heterogeneous etiologies and the insidious nature of this disease makes early diagnosis implausible and it could be argued that collectively, institutions and industry have not given enough validation to attempts to implement a wide enough aperture in tackling the problem. Recent approvals, of course, have given the field some hope that we might be on a path to discovering how this disease evolves and how we can intervene far earlier with the help of more robust biomarkers, helping to stratify patients in clinical trials and ultimately diagnose and treat the disease much earlier.

Most of the research in recent years has focused on the traditional protein tau–beta amyloid hypothesis, but other groups are now looking beyond these approaches at the function and role of the brain microbiome, which has been overlooked mainly because there was no consensus that the brain played host to microbes. Evidence seems to be shifting with cases of patients with cognitive decline and memory loss having their infections treated and symptoms reversed. Other historical, neglected theories relating to the accumulation of fat droplets in brain immune cells are also starting to gain traction as a new avenue for therapeutic development. Malfunctioning mitochondria and its impact on the progression of the disease is also being investigated and only recently we’ve heard about how light and sound may be able to trigger and optimize the brain’s waste disposal system.

These advancements are indeed promising, and new approvals will stem the tide of disease progression in early onset indications, but of course we have a long road to tread as we continue to learn. To fully understand how the billions of cells and neurons function in the brain in both healthy and diseases states, we need a better understanding of the sequence of events in the development of Alzheimer’s disease and indeed of neuronal diversity. This is where single cell technologies have been transformative in helping illuminate the spatial organization and function of these cells, giving a clearer idea of the circuitry in the brain and a broader understanding of how brain cells vary between individuals. Embracing a large-scale omics approach will help us explore our fairly limited knowledge of the difference in sexes, with women being disproportionately affected by the disease. As we continue to employ precision medicine strategies to this inscrutable disease, building a broader picture of the disease and creating more varied data on different subsets of the disease, we may in time develop more powerful diagnostics that can identify patients much earlier and reduce the burden on society, but most importantly, on patients and families. The incredible rapid evolution of the human brain with its underlying complexity has ultimately left it very vulnerable to these ancient genetic changes—but these very same changes that led to our great intelligence will help find a solution in the near distant future.

Damian Doherty

Editor in Chief
Inside Precision Medicine