TY - JOUR
T1 - MAP-2 immunolabeling can distinguish diffuse from dense-core amyloid plaques in brains with Alzheimer's disease
AU - D'Andrea, Michael R.
AU - Nagele, R. G.
N1 - Funding Information:
We thank the excellntehisolotgcal ianidmuo-nm histochemical expertise of P.A. Reiser (BS, MT, HT; ASCP), N.A. Gumula (HT; ASCP), B.M. Hertzog (BS, MT; ASCP) and D. Polkovitch (BS, HT; ASCP) of The R.W. Johnson Pharmaceutical Research Institute’s MorphoMetrics Department. Supported in part by a grant from The National Institute on Ang (gAG00i925).
Funding Information:
Postmortem sporadic entorhinal cortex and hippocampus tissues from patients suffering from Alzheimer’s disease (n ˆ 14, mean age ˆ79.8 11.1 year; mean postmortem time interval ˆ 4.3 1.8 h) and age-matched, nondemented control brains (n ˆ 5, mean age ˆ 76.4 8.4 year; mean postmortem time interval ˆ 4.6 1.4 h) were obtained from the Harvard Brain TssueiRsourcee Center (HBTRC, Belmont, MA). The HBTRC is supported in part by a Public Health Service grant MH/NS 31862. Postmortem pathological con®rma-tion of AD was carried out for each AD brain specimen. The neuropathology in each of the brains included in this study was documented by board certi®ed neuropathologists, as described previously (D’Andrea et al. 2001a,b, Nagele et al. 2001, Wang et al. 2001). Tissues were trmmei d and processed for paraf®n emdding.bFeveiicron-mscets iworene serially cut and mounted on SuperFrost Plus‡ (Fisher Scienti®c, Pittsburgh, PA) microscopy sdls ie and drediovernight.
PY - 2002
Y1 - 2002
N2 - 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 (Aβ42) 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 Aβ42-positive diffuse plaques in AD brains. In contrast, analysis of serial sections revealed that MAP-2 was absent from Aβ42-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.
AB - 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 (Aβ42) 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 Aβ42-positive diffuse plaques in AD brains. In contrast, analysis of serial sections revealed that MAP-2 was absent from Aβ42-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.
UR - http://www.scopus.com/inward/record.url?scp=0036268118&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036268118&partnerID=8YFLogxK
U2 - 10.1080/bih.77.2.95.103
DO - 10.1080/bih.77.2.95.103
M3 - Article
C2 - 12083391
AN - SCOPUS:0036268118
SN - 1052-0295
VL - 77
SP - 95
EP - 103
JO - Biotechnic and Histochemistry
JF - Biotechnic and Histochemistry
IS - 2
ER -