RELATIONSHIP BETWEEN APOLIPOPROTEIN-E AND THE AMYLOID DEPOSITS AND DYSTROPHIC NEURITES OF ALZHEIMERS-DISEASE

Although the inheritance of certain apolipoprotein E (ApoE) alleles ha s been recognized as a genetic risk factor for Alzheimer's disease, th e role of ApoE in the pathology underlying this disease is unclear. Se veral reports have emphasized the association of ApoE with either beta -amyloid plaque formation or the development of neurofibrillary pathol ogy. Utilization of multiple label immunohistochemical methods enabled us to examine directly the localization of ApoE immunoreactivity rela tive to beta-amyloid plaques, dystrophic neurites and neurofibrillary tangles. In Alzheimer's disease cases, beta-amyloid plaques showing hi gh ApoE immunoreactivity were localized to layers II, Ill and V of the neocortex. In layer I, beta-amyloid plaques were unlabelled for ApoE relative to beta-amyloid. Dense core plaques labelled for beta-amyloid often had only the central portions labelled for ApoE. Conversely Apo E labelled spherical structures within some plaques were not immunorea ctive for beta-amyloid or dystrophic neurite markers. Unlike beta-amyl oid labelled plaques, all ApoE immunoreactive plaques were associated with dystrophic neurites. In preclinical Alzheimer's disease cases, mo st plaques were double labelled for beta-amyloid and ApoE. ApoE did no t label dystrophic neurites or the early stages of neurofibrillary tan gle formation, indicating that ApoE may not be directly involved in ne urofibrillary pathology. The specific presence of ApoE in plaques asso ciated with dystrophic neurites in demented patients suggests that Apo E may contribute toward a higher degree of beta-amyloid fibrillogenesi s, enhancing the ability of certain plaques to cause damage to surroun ding axons.