The immunohistochemical findings of a small study of 6 AD brains suggesting that calbindin-immunopositive neurons are relatively preserved in cases with moderate amyloid plaque and neurofibrillary content but are lost in more severe cases [94] prompts the question of whether CSF calbindin levels would be more significantly elevated in more severely demented individuals. This evidence concerns the gene CALB1 and Alzheimer disease.