Genetic causes of degenerative dementia from an evolutionary perspective

Estrella Gómez Tortosa

Degenerative dementias are unique to humans and appear in post-reproductive age, which excludes natural selection. From an evolutionary point of view we could classify them into two etiological groups. The first is associated to a specific genetic mutation, which occurred by chance in a founder, and further transmitted through generations. This genetic alteration leads to dysfunction in specific neuronal circuits, which manifests as a recognizable clinical syndrome. Advances in molecular diagnostics have already identified about twenty genes whose mutations cause these dementias, allowing genetic counseling to prevent future transmission.

Within the second group, Alzheimer's disease (AD) with senile onset would be the paradigm. It occurs in the context of longevity, probably associated with a group of genetic variants that confer increased susceptibility to aging. It is likely that senile AD is a consequence of intelligence and a prolonged learning ability of human beings. The development of a complex cerebral cortex at both neuronal and synaptic levels, which maintains plasticity for decades at the expense of a high metabolic cost, can lead to a neurodegenerative process in those individuals, who are the most long-lived and bear genetic susceptibility variants.

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