[Alzheimer's disease and brain evolution: is Alzheimer's disease an example of antagonistic pleiotropy?].
BACKGROUND
Alzheimer's disease (AD) appears to be exclusive to our species. This suggests a relationship between the disease and genetic, functional and structural changes that have taken place throughout the evolution of the human brain.


METHODS
The expression of genes linked to neurotransmission, neuroplasticity, axonal transport, aerobic metabolism and neuroprotection seems to have increased within the human cerebral cortex and such phenomena represent adaptations that induce greater neuronal activity throughout a long lifespan. High levels of neuroplasticity increase neuronal vulnerability to factors capable of triggering the lesions that are typically found in AD. Several genes related to increased neuronal activity are extremely vulnerable to factors related to old age, such as oxidative stress. Some kind of dysfunction in such genes can disrupt proper regulation of a number of pathways (neuroplasticity, axonal transport) and promote the abnormal accumulation of peptides that is characteristic of AD. Possessing certain polymorphisms of neuroprotective genes or of the electron transport chain could afford protection against AD. Increased intake of animal fats could alter the balance of polyunsaturated fatty acids in the neuronal membrane and favour a higher susceptibility to oxidative stress.


CONCLUSIONS
AD could constitute an example of antagonistic pleiotropy: the increased expression of advantageous genes at an early age could turn out to be harmful at an advanced age.
Bufill
E
E
Unidad de Neurología, Servicio de Medicina Interna, Hospital General de Vic, Vic, Barcelona, Spain. ebufill@eresmas.com
Blesa
R
R
D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D005075:Biological Evolution; D001921:Brain / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D018384:Oxidative Stress