MAP-2 immunolabeling can distinguish diffuse from dense-core amyloid plaques in brains with Alzheimer's disease.
Alzheimer's disease (AD) neuropathology is characterized by the presence of diffuse and dense-core (neuritic) amyloid plaques in specific areas of the brain. The origin of these plaques and the relationship between them is poorly understood. Current methods to identify clearly these types of plaques in the AD brains are largely dependent upon morphological characteristics. Dense-core amyloid plaques in the entorhinal cortex and hippocampus of AD brains might arise from the lysis of neurons overburdened by excessive intracellular deposition of amyloid beta1-42 (Abeta42) peptide. The local release of active lysosomal enzymes, which persist within these plaques, might degrade most of the released intracellular proteins, leaving behind only those that are resistant to proteolytic digestion, such as ubiquitin, tau, neurofilament proteins and amyloid. To test the possibility that proteins that are sensitive to proteolysis may be degraded selectively in plaques, we used immunohistochemistry to examine the distribution of microtubule-associated protein-2 (MAP-2), a protein localized primarily in neuronal dendrites and known to be sensitive to proteolysis. Uniform MAP-2 immunolabeling was detected throughout the somatodendritic compartment of neurons in age-matched control cortical brain tissues as well as throughout areas of Abeta42-positive diffuse plaques in AD brains. In contrast, analysis of serial sections revealed that MAP-2 was absent from Abeta42-positive dense-core plaques in AD brains. Our results indicate that this differential MAP-2 immunolabeling pattern among plaques may be employed as a reliable and sensitive method to distinguish dense-core plaques from diffuse plaques within AD brain tissue. Furthermore, this biochemical distinction indicates that dense-core and diffuse plaques are formed by different mechanisms.
D'Andrea
M R
MR
The R. W. Johnson Pharmaceutical Research Institute, Drug Discovery, Spring House, Pennsylvania 19477, USA. mdandrea@prius.jnj.com
Nagele
R G
RG
D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology; D015415:Biomarkers; D018728:Entorhinal Cortex / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000032:analysis*; D058225:Plaque, Amyloid / Q000145:classification* / Q000473:pathology*
D015415:Biomarkers; D008869:Microtubule-Associated Proteins