BRAIN EXPRESSION OF APOLIPOPROTEIN-E, APOLIPOPROTEIN-J, AND APOLIPOPROTEIN-A-I IN ALZHEIMERS-DISEASE

Inheritance of the epsilon 4 allele of apolipoprotein (apo) E is assoc iated with increased risk of Alzheimer's disease (AD) and with increas ed beta-amyloid peptide (A beta) deposition in the cortex. Apo E is a member of a family of exchangeable apos, characterized by the presence of amphipathic alpha-helical segments that allow these molecules to a ct as surfactants on the surface of lipoprotein particles. Two members of this family, apo E and apo J, have been shown to bind soluble A be ta, and both are associated with senile plaques in the AD cortex. We n ow have studied the pattern of brain apo expression and found that fiv e members of this class are present: apo AI, A-IV, D, E, and J, By con trast, apos A-II, B, and C-II were not detectable. Immunohistochemistr y revealed that, in addition to apo E and apo J, apo A-I immunostained occasional senile plaques in AD cortex. Immunoblot analysis showed no difference in the relative amounts of any of these apos in tissue hom ogenates of frontal lobe from AD or control patients. Comparison by AP O E genotype showed no differences in the amount of apo E in brain amo ng APO E epsilon 3/3, epsilon 3/4, or epsilon 4/4 individuals; however , a significant decrease in the amount of apo J was associated with th e APO E epsilon 4 allele. No differences in apo J levels were detected in CSF samples of AD subjects, We propose that several members of the exchangeable apo family may interact with A beta deposits in senile p laques through common amphipathic alpha-helical domains. Competition a mong these molecules for binding of A beta or A beta aggregates may in fluence the deposition of A beta in senile plaques.