Effect of apolipoprotein E on neurite outgrowth and beta-amyloid-induced toxicity in developing rat primary hippocampal cultures.
The correlation between the epsilon 4 allele of apolipoprotein E (apoE) and Alzheimer's disease is well established. However, the role of apoE in normal as well as pathological brain processes remains unclear. We evaluated the effect of apoE treatment on development and beta-amyloid (A beta)-induced toxicity using primary cultures of developing rat hippocampal neurons. The source of apoE was conditioned media from HEK cells stably transfected with human apoE3 or apoE4 cDNA, a preparation where apoE is lipid-associated. Morphological and biochemical changes in the cultures were assessed at 1 and 3 days following low- and high-density plating with either apoE3 or E4 with or without A beta. Both apoE isoforms were neurotrophic, as measured by increased neurite length. Aged A beta(1-42), a peptide preparation exhibiting extensive fibril and aggregate formation, is toxic to these cultures. Addition of apoE3 and E4 significantly and comparably attenuated the A beta-induced reduction in both neurite length and cell viability. The level of protection against this toxicity was proportional to the neurotrophic actions of the two apoE isoforms. Thus, apoE acts as a potent growth factor in both the absence and the presence of A beta, supporting a potentially important role for apoE in neurobiology.
Puttfarcken
P S
PS
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Manelli
A M
AM
Falduto
M T
MT
Getz
G S
GS
LaDu
M J
MJ
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000737:chemistry / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D007536:Isomerism; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D017077:Culture Media, Conditioned; D018696:Neuroprotective Agents