Buried Treasure? Overlooked and Newly Discovered Evolutionary Contributions to Human Brain Diseases

Abstract

Clinical neuroscience focuses on the mechanisms of brain function, but this approach falls short of insights into how the central nervous system (CNS) evolved, both in health and disease. Here, we discuss evolutionary concepts relevant to understanding human brain diseases, on the genetic, subcellular, cellular, connectomic, behavioral, and cultural levels. By revisiting common neurological diseases, we discuss evolved residues from our ancestors, mechanisms of exaptation, antagonistic pleiotropy, and human longevity with the consequent outpacing of biological evolution by cultural evolution. An evolution-based conceptual framework can propel transdisciplinary research targeting the constraints imposed by and compensatory adaptations involved in human-specific neurological diseases. ANN NEUROL 2025;98:1178-1195.

FIGURE 1

Comparison of the human, vervet, and rat brains (from left to right). The 3 species show both similarities in their bauplan, but also remarkable differences. For example, whereas the internal structure of the hippocampus seems to be quite similar, its localization in the brain differs significantly between the human and the vervet brain against the rat brain. The proportion of white matter is larger in the human brain than in the vervet brain than in the rat brain. Please note the different sizes of the scale bars.

FIGURE 2

Tree symbolizing factors contributing to the global human evolution. The left‐sided branches indicate various factors of the biological evolution, and the right‐sided branches indicate various factors of the sociocultural evolution.