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Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA Drs. Arriagada and Hedley-Whyte)
Department Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (Drs. Growdon and Hyman).
We studied the accumulation of neurofibrillary tangles (NFTs) and senile plaques (SPs) in 10 Alzheimer's disease patients who had been examined during life. We counted NFTs and SPs in 13 cytoarchitectural regions representing limbic, primary sensory, and association cortices, and in subcortical neurotransmitter-specific areas. The degree of neuropathologic change was compared with the severity of dementia, as assessed by the Blessed Dementia Scale and duration of illness. We found that (1) the severity of dementia was positively related to the number of NFTs in neocortex, but not to the degree of SP deposition; (2) NFTs accumulate in a consistent pattern reflecting hierarchic vulnerability of individual cytoarchitectural fields; (3) NFTs appeared in the entorhinal cortex, CA1/subiculum field of the hippocampal formation, and the amygdala early in the disease process; and (4) the degree of SP deposition was also related to a hierarchic vulnerability of certain brain areas to accumulate SPs, but the pattern of SP distribution was different from that of NFT.
Address correspondence and reprint requests to Dr. Bradley T. Hyman, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114.
Presented in part at the 41st annual meeting of the American Academy of Neurology, Boston, MA, April 1991.
Supported by NIH grants AG08487, P50 AG05134, the Seevak-Hoffman fund, and the Brookdale Foundation.
Received July 30, 1991. Accepted for publication in final form August 28, 1991.
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G. Binetti, J. J. Locascio, S. Corkin, J. P. Vonsattel, and J. H. Growdon Differences Between Pick Disease and Alzheimer Disease in Clinical Appearance and Rate of Cognitive Decline Arch Neurol, February 1, 2000; 57(2): 225 - 232. [Abstract] [Full Text] [PDF]
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V. M. Moceri, W. A. Kukull, I. Emanuel, G. van Belle, and E. B. Larson Early-life risk factors and the development of Alzheimer's disease Neurology, January 25, 2000; 54(2): 415 - 415. [Abstract] [Full Text] [PDF]
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 A Abraha, N Ghoshal, T. Gamblin, V Cryns, R. Berry, J Kuret, and L. Binder C-terminal inhibition of tau assembly in vitro and in Alzheimer's disease J. Cell Sci., January 11, 2000; 113(21): 3737 - 3745. [Abstract] [PDF]
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G. Hall, B Chu, G Lee, and J Yao Human tau filaments induce microtubule and synapse loss in an in vivo model of neurofibrillary degenerative disease J. Cell Sci., January 4, 2000; 113(8): 1373 - 1387. [Abstract] [PDF]
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P. D. Mehta, T. Pirttila, S. P. Mehta, E. A. Sersen, P. S. Aisen, and H. M. Wisniewski Plasma and Cerebrospinal Fluid Levels of Amyloid {beta} Proteins 1-40 and 1-42 in Alzheimer Disease Arch Neurol, January 1, 2000; 57(1): 100 - 105. [Abstract] [Full Text] [PDF]
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I. Grundke-Iqbal and K. Iqbal Tau Pathology Generated by Overexpression of Tau Am. J. Pathol., December 1, 1999; 155(6): 1781 - 1785. [Full Text] [PDF]
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J. K. Johnson, E. Head, R. Kim, A. Starr, and C. W. Cotman Clinical and Pathological Evidence for a Frontal Variant of Alzheimer Disease Arch Neurol, October 1, 1999; 56(10): 1233 - 1239. [Abstract] [Full Text] [PDF]
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N. Ghoshal, J. F. Smiley, A. J. DeMaggio, M. F. Hoekstra, E. J. Cochran, L. I. Binder, and J. Kuret A New Molecular Link between the Fibrillar and Granulovacuolar Lesions of Alzheimer's Disease Am. J. Pathol., October 1, 1999; 155(4): 1163 - 1172. [Abstract] [Full Text] [PDF]
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C. R. Jack Jr., R. C. Petersen, Y. C. Xu, P. C. O'Brien, G. E. Smith, R. J. Ivnik, B. F. Boeve, S. C. Waring, E. G. Tangalos, and E. Kokmen Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment Neurology, April 1, 1999; 52(7): 1397 - 1397. [Abstract] [Full Text] [PDF]
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G. Marcon, G. Giaccone, B. Canciani, L. Cajola, G. Rossi, L. De Gioia, M. Salmona, O. Bugiani, and F. Tagliavini A ßPP Peptide Carboxyl-Terminal to Aß Is Neurotoxic Am. J. Pathol., April 1, 1999; 154(4): 1001 - 1007. [Abstract] [Full Text] [PDF]
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 O. Felician and T. A. Sandson The Neurobiology and Pharmacotherapy of Alzheimer's Disease J Neuropsychiatry Clin Neurosci, February 1, 1999; 11(1): 19 - 31. [Abstract] [Full Text]
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P.-T. Xu, J. R. Gilbert, H.-L. Qiu, J. Ervin, T. R. Rothrock-Christian, C. Hulette, and D. E. Schmechel Specific Regional Transcription of Apolipoprotein E in Human Brain Neurons Am. J. Pathol., February 1, 1999; 154(2): 601 - 611. [Abstract] [Full Text] [PDF]
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K. Juottonen, M. P. Laakso, K. Partanen, and H. Soininen Comparative MR Analysis of the Entorhinal Cortex and Hippocampus in Diagnosing Alzheimer Disease AJNR Am. J. Neuroradiol., January 1, 1999; 20(1): 139 - 144. [Abstract] [Full Text]
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P. Friedhoff, M. von Bergen, E.-M. Mandelkow, P. Davies, and E. Mandelkow A nucleated assembly mechanism of Alzheimer paired helical filaments PNAS, December 22, 1998; 95(26): 15712 - 15717. [Abstract] [Full Text] [PDF]
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A. Kinoshita, M. Kinoshita, H. Akiyama, H. Tomimoto, I. Akiguchi, S. Kumar, M. Noda, and J. Kimura Identification of Septins in Neurofibrillary Tangles in Alzheimer's Disease Am. J. Pathol., November 1, 1998; 153(5): 1551 - 1560. [Abstract] [Full Text] [PDF]
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B. T. Hyman New Neuropathological Criteria for Alzheimer Disease Arch Neurol, September 1, 1998; 55(9): 1174 - 1176. [Full Text] [PDF]
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V. Haroutunian, D. P. Perl, D. P. Purohit, D. Marin, K. Khan, M. Lantz, K. L. Davis, and R. C. Mohs Regional Distribution of Neuritic Plaques in the Nondemented Elderly and Subjects With Very Mild Alzheimer Disease Arch Neurol, September 1, 1998; 55(9): 1185 - 1191. [Abstract] [Full Text] [PDF]
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M. J. McNamara, T. Gomez-Isla, and B. T. Hyman Apolipoprotein E Genotype and Deposits of A{beta}40 and A{beta}42 in Alzheimer Disease Arch Neurol, July 1, 1998; 55(7): 1001 - 1004. [Abstract] [Full Text] [PDF]
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S. Craft, L. Teri, S. D. Edland, W. A. Kukull, G. Schellenberg, W. C. McCormick, J. D. Bowen, and E. B. Larson Accelerated decline in apolipoprotein E-{epsilon}4 homozygotes with Alzheimer's disease Neurology, July 1, 1998; 51(1): 149 - 153. [Abstract] [Full Text] [PDF]
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M. G. Spillantini, J. R. Murrell, M. Goedert, M. R. Farlow, A. Klug, and B. Ghetti Mutation in the tau gene in familial multiple system tauopathy with presenile dementia PNAS, June 23, 1998; 95(13): 7737 - 7741. [Abstract] [Full Text] [PDF]
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P. Giannakopoulos, M. Duc, G. Gold, P. R. Hof, J.-P. Michel, and C. Bouras Pathologic Correlates of Apraxia in Alzheimer Disease Arch Neurol, May 1, 1998; 55(5): 689 - 695. [Abstract] [Full Text] [PDF]
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P. J. Yao and P. D. Coleman Reduction of O-Linked N-Acetylglucosamine-Modified Assembly Protein-3 in Alzheimer's Disease J. Neurosci., April 1, 1998; 18(7): 2399 - 2411. [Abstract] [Full Text] [PDF]
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N Andreasen, E Vanmechelen, A Van de Voorde, P Davidsson, C Hesse, S Tarvonen, I Raiha, L Sourander, B Winblad, and K Blennow Cerebrospinal fluid tau protein as a biochemical marker for Alzheimer's disease: a community based follow up study J. Neurol. Neurosurg. Psychiatry, March 1, 1998; 64(3): 298 - 305. [Abstract] [Full Text] [PDF]
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L. Berg, D. W. McKeel Jr, J. P. Miller, M. Storandt, E. H. Rubin, J. C. Morris, J. Baty, M. Coats, J. Norton, A. M. Goate, et al. Clinicopathologic Studies in Cognitively Healthy Aging and Alzheimer Disease: Relation of Histologic Markers to Dementia Severity, Age, Sex, and Apolipoprotein E Genotype Arch Neurol, March 1, 1998; 55(3): 326 - 335. [Abstract] [Full Text] [PDF]
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J. H. Morrison and P. R. Hof Life and Death of Neurons in the Aging Brain Science, October 17, 1997; 278(5337): 412 - 419. [Abstract] [Full Text]
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M. Hong, D. C. R. Chen, P. S. Klein, and V. M.-Y. Lee Lithium Reduces Tau Phosphorylation by Inhibition of Glycogen Synthase Kinase-3 J. Biol. Chem., October 3, 1997; 272(40): 25326 - 25332. [Abstract] [Full Text] [PDF]
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M. C. Irizarry, F. Soriano, M. McNamara, K. J. Page, D. Schenk, D. Games, and B. T. Hyman Abeta Deposition Is Associated with Neuropil Changes, but not with Overt Neuronal Loss in the Human Amyloid Precursor Protein V717F (PDAPP) Transgenic Mouse J. Neurosci., September 15, 1997; 17(18): 7053 - 7059. [Abstract] [Full Text] [PDF]
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M. Hong and V. M.-Y. Lee Insulin and Insulin-like Growth Factor-1 Regulate Tau Phosphorylation in Cultured Human Neurons J. Biol. Chem., August 1, 1997; 272(31): 19547 - 19553. [Abstract] [Full Text] [PDF]
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L. Cruz, B. Urbanc, S. V. Buldyrev, R. Christie, T. Gomez-Isla, S. Havlin, M. McNamara, H. E. Stanley, and B. T. Hyman Aggregation and disaggregation of senile plaques in Alzheimer disease PNAS, July 8, 1997; 94(14): 7612 - 7616. [Abstract] [Full Text] [PDF]
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