Comparative anatomic data suggest that several systems of brain regions underwent selective expansion or differentiation during primate evolution, according to the principle of 'integrated phylogeny'. This involved expansion of the neocortex. Certain human neurodegenerative diseases, including Alzheimer disease, affect such systems, suggesting that they are 'phylogenic' diseases and that the genetic changes that promoted integrated phylogeny are related to the genetics of these diseases. Studies of monozygotic twins discordant and discordant for Alzheimer disease suggest heritable as well as not evidently heritable forms of this disorder, consistent with genetic heterogeneity. Measurements of brain blood flow using positron emission tomography, during cognitive stimulation, suggest that reversible synaptic failure underlies early functional deficits in Alzheimer disease. The critical temperature for maintaining stable lipid monolayers in vitro is reduced from 37 degrees C to less than 30 degrees C, using lipids from temporal association but not cerebellar cortex of Alzheimer brain, suggesting that cell membrane instability in vulnerable brain regions contributes to progression of Alzheimer disease.
