Early intraneuronal Abeta deposition in the hippocampus of APP transgenic mice.
Increasing evidence suggests that intraneuronal amyloid-beta (Abeta) accumulation may be an early event in Alzheimer's disease (AD) pathogenesis. However direct in vivo evidence regarding initial Abeta seeding is missing. Using an APP transgenic mouse model, our sensitive immunocytochemical procedures revealed a novel intraneuronal Abeta deposition in the somas of hippocampal CA1/subiculum neurons far in advance of the occurrence of extracellular Abetaplaques. These deposits increased exponentially with age and were elevated approximately 4-fold (p < 0.001) by high fat/high cholesterol diet. Abeta40 and Abeta42 were the major constituents of these deposits and were co-localized with lysosomal markers. Our results are consistent with the notion that the earliest Abeta deposition occurs intraneuronally, prior to extracellular amyloid plaque formation.
Shie
Feng-Shiun
FS
Department of Pathology, University of Washington, School of Medicine, Seattle, WA 98195-7490, USA.
LeBoeuf
Renée C
RC
Jin
Lee-Way
LW
LeBoeur
Renée C
RC
D000375:Aging / Q000378:metabolism; D019943:Amino Acid Substitution; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002791:Cholesterol, Dietary / Q000633:toxicity; D003433:Crosses, Genetic; D004041:Dietary Fats / Q000633:toxicity; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D007424:Intracellular Fluid / Q000737:chemistry; D008247:Lysosomes / Q000737:chemistry / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D020125:Mutation, Missense; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D017354:Point Mutation
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002791:Cholesterol, Dietary; D004041:Dietary Fats