Abstract
Acetylcholinesterase and butyrylcholinesterase have been associated with structures undergoing neurofibrillary degeneration, as well as with all types of senile plaques, in non-demented aged and Alzheimer's brains. At the electron microscope level, the reaction product of both enzymes, appeared to decorate paired helical filaments, straight filaments and βA4 amyloid fibrils. Recent studies showed that cholinesterases were associated with amyloid at early stages, e.g., in diffuse plaques. In the present study, the interrelationship of cholinesterases to structures undergoing neurofibrillary degeneration was analyzed further. Tau immunoreactivity was compared to the staining pattern observed with the two esterases. Double protocols consecutively performed on the same sections, and counterstaining with thioflavin-S, confirmed the presence of cholinesterases in all structures with neurofibrillary degeneration. The conclusion that cholinesterases consistently colocalize with both neurofibrillary bundles and βA4 amyloid fibrils at all stages of their accumulation, allows us to speculate on the possible role that these enzymes may play in either the formation or the consolidation of fibrillary aggregates.
Similar content being viewed by others
References
Adams JC (1977) Technical considerations of the use of horseradish peroxidase as a neuronal marker. Neuroscience 2: 141–145
Akiyama H, Ikeda K, Kondo H, McGeer PL (1992). Thrombin accumulation in brains of patients with Alzheimer's disease. Neurosci Lett 146: 152–154
Anderton BH, Breinburg D, Downes MJ, Green PJ, Tomlinson BE, Ulrich J, Wood JN, Kahn J (1982) Monoclonal antibodies show that neurofibrillary tangles and neurofilaments share antigenic determinants. Nature 298: 84–86
Bancher C, Brunner C, Lassmann H, Budka H, Jellinger K, Wiche G, Seitelberger F, Grundke-Iqbal I, Iqbal K, Wisniewski HM (1989) Accumulation of abnormally phosphorylated τ precedes the formation of neurofibrillary tangles in Alzheimer's disease. Brain Res 477: 90–99
Bondareff W, Wischik CM, Novak M, Amos WB, Klug A, Roth M (1990) Molecular analysis of neurofibrillary degeneration in Alzheimer's disease. Am J Pathol 137: 711–723
Carson KA, Geula C, Mesulam M-M, (1991) Electron microscopic localization of cholinesterase activity in Alzheimer brain tissue. Brain Res 540: 204–208
Chatonnet A, Lockridge O (1989) Comparison of butyrylcholinesterase and acetylcholinesterase. Biochem J 260: 625–634
Chubb IW, Hodgson AJ, White GH (1980) Acetylcholinesterase hydrolyzes substance P. Neuroscience 5: 2065–2072
Chubb IW, Ranieri E, White GH, Hodgson A (1983) The enkephalins are amongst the peptides hydrolyzed by purified acetylcholinesterase. Neuroscience 10: 1369–1377
Coleman AE, Geula C, Price BH, Mesulam M-M (1992) Differential laminar distribution of acetylcholinesterase and butyrylcholinesterase containing tangles in the cerebral cortex of Alzheimer's disease. Brain Res 596: 340–344
Duong T, Pommier EC, Scheibel AB (1989) Immunodetection of the amyloid P component in Alzheimer's disease. Acta Neuropathol 78: 429–437
Friede RL (1965) Enzyme histochemical studies of senile plaques. J Neuropathol Exp Neurol 24: 477–491
Geddes JW, Monaghan DT, Cotman CW, Lott IT, Kim RC, Chui HC (1985) Plasticity of hippocampal circuitry in Alzheimer's disease. Science 230: 1179–1181
Gómez-Ramos P, Mufson EJ, Morán MA (1992) Ultrastructural localization of acetylcholinesterase in neurofibrillary tangles, neuropil threads and senile plaques in aged and Alzheimer's brain. Brain Res 569: 229–237
Grundke-Iqbal I, Iqbal K, Quinlan M, Tung Y-C, Zaidi MS, Wisniewski HM (1986) Microtubule-associated protein tau: a component of Alzheimer paired helical filaments. J Biol Chem 261: 6084–6089
Guiroy DC, Miyazaki M, Multhaup G Fischer P, Garruto RM, Beyreuther K, Masters CL, Simms G, Gibbs CJ Jr, Gajdusek DC (1987) Amyloid neurofibrillary tangles of Guamanian Parkinsonism-dementia and Alzheimer disease share identical amino acid sequence. Proc Natl Acad Sci USA 84: 2073–2077
Joachim CL, Morris JH, Selkoe DS, Kosik KS (1987) Tau epitopes are incorporated into a range of lesions in Alzheimer's disease. J Neuropath Exp Neurol 46: 611–622
Karnovsky MJ, Roots L (1964) A “direct-coloring”, thiocholine method for cholinesterases. J Histochem Cytochem 12: 219–221
Khachaturian ZS (1985) Diagnosis of Alzheimer's disease. Arch Neurol 42: 1097–1105
Kosik KS, Duffy LK, Dowling MM, Abraham C, McCluskey A, Selkoe DJ (1984) Microtubule-associated protein 2: monoclonal antibodies demonstrate the selective incorporation of certain epitopes into Alzheimer neurofibrillary tangles. Proc Natl Acad Sci USA 81: 7941–7945
Kosik KS, Joachim CL, Selkoe DJ (1986) Microtubule-associated protein tau (τ) is a major antigenic component of paired helical filaments in Alzheimer disease. Proc Natl Acad Sci USA 83: 4044–4048
Kosik KS, Orecchio LD, Binder L, Trojanowski JQ, Lee VM-Y, Lee G (1988) Epitopes that span the tau molecule are shared with paired helical filaments. Neuron 1: 817–825
Kosik KS, Crandall JE, Mufson EJ, Neve RL (1989) Tau in situ hybridization in normal and Alzheimer brain: localization in the somatodendritic compartment. Ann Neurol 26: 352–361
Kosik KS, Kowall NW, McKee AC (1989) Along the way to a neurofibrillary tangle: a look at the structure of tau. Ann Med 21: 109–112
Kowall NW, Kosik KS (1987) Axonal disruption and aberrant localization of tau protein characterize the neuropil pathology of Alzheimer's disease. Ann Neurol 22: 639–643
Lockridge O (1982) Substance P hydrolysis by human serum cholinesterase. J Neurochem 39: 106–110
Masters CL, Multhaup G, Simms G, Pottgiesser J, Martins RN, Beyreuther K (1985) Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J 4: 2757–2763
McKee AC, Kowall NW, Kosik KS (1989) Microtubular reorganization and dendritic growth response in Alzheimer's disease. Ann Neurol 26: 652–659
McKee AC, Kosik KS, Kowall NW (1991) Dystrophic neurites precede neurofibrillary tangle formation and mark the progression of dementia in Alzheimer's disease. J Neuropathol Exp Neurol 50: 315
McKee AC, Kosik KS, Kowall NW (1991) Neuritic pathology and dementia in Alzheimer's disease. Ann Neurol 30: 156–165
Mesulam M-M, Geula C (1991) Acetylcholinesterase-rich neurons of the human cerebral cortex: cytoarchitectonic and ontogenetic patterns of distribution. J Comp Neurol 306: 193–220
Mesulam M-M, Geula C (1991) Differential distribution of a neurofilament protein epitope in acetylcholinesterase-rich neurons of human cerebral neocortex. Brain Res 544: 169–173
Mesulam M-M, Morán MA (1987) Cholinesterases within neurofibrillary tangles related to age and Alzheimer's disease. Ann Neurol 22: 223–228
Mesulam M-M, Geula C, Morán MA (1987) Anatomy of cholinesterase inhibition in Alzheimer's disease: effect of physostigmine and tetrahydroaminoacridine on plaques and tangles. Ann Neurol 22: 683–691
Morán MA, Gómez-Ramos P (1992) Cholinesterase histochemistry in the human brain: effect of various fixation and storage conditions. J Neurosci Methods 43: 49–54
Morán MA, Mufson EJ, Gómez-Ramos P (1993) Colocalization of cholinesterases with β amyloid protein in aged and Alzheimer's brains. Acta Neuropathol 85: 362–369
Mori H, Kondo J, Ihara Y (1987) Ubiquitin is a component of paired helical filaments in Alzheimer's disease. Science 235: 1641–1644
Nukina N, Ihara Y (1986) One of the antigenic determinants of paired helical filaments is related to tau protein. J Biochem 99: 1541–1544
Ogane N, Giacobini E, Struble R (1992) Differential inhibition of acetylcholinesterase molecular forms in normal and Alzheimer disease brain. Brain Res 589: 307–312
Perry G, Friedman R, Shaw G, Chau V (1987) Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brain. Proc Natl Acad Sci USA 84: 3033–3036
Perry G, Siedlak SL, Richey P, Kawai M, Cras P, Kalaria RN, Galloway PG, Scardina JM, Cordell B, Greenberg BD, Ledbetter SR, Gambetti P (1991) Association of heparan sulfate proteoglycan with the neurofibrillary tangles of Alzheimer's Disease. J Neurosci 11: 3679–3683
Pollock NJ, Wood JG (1988) Differential sensitivity of the microtubule-associated protein, tau, in Alzheimer's disease tissue to formalin fixation. J Histochem Cytochem 36: 1117–1121
Probst A, Langui D, Lautenschlager C, Ulrich J, Brion JP, Anderton BH (1988) Progressive supranuclear palsy: extensive neuropil threads in addition to neurofibrillary tangles. Very similar antigenicity of subcortical neuronal pathology in progressive supranuclear palsy and Alzheimer's disease. Acta Neuropathol 77: 61–68
Rasool CG, Svendsen CN, Selkoe DJ (1986) Neurofibrillary degeneration of cholinergic and noncholinergic neurons of the basal forebrain in Alzheimer's disease. Ann Neurol 20: 482–488
Shimohama S, Homma Y, Suenaga T, Fujimoto S, Taniguchi T, Araki W, Yamaoka Y, Takenawa T, Kimura J (1991) Aberrant accumulation of phospholipase C-delta in Alzheimer brains. Am J Pathol 139: 737–742
Small DH, Ismael Z, Chubb IW (1987) Acetylcholinesterase exhibits trypsin-like and metalloexopeptidase-like activity in cleaving a model peptide. Neuroscience 21: 991–995
Small DH, Moir RD, Fuller SJ, Michaelson S, Bush AJ, Li Q-X, Milward E, Hilbich C, Weidemann A, Beyreuther K, Masters CL (1991) A protease activity associated with acetylcholinesterase releases the membrane-bound form of the amyloid protein precursor of Alzheimer's disease. Biochemistry 30: 10795–10799
Snow AD, Mar H, Nochlin D, Sekiguchi RT, Kimata K, Koike Y, Wight TN (1990) Early accumulation of heparan sulfate in neurons and the beta-amyloid protein containing lesions of Alzheimer's disease and Down's syndrome. Am J Pathol 137: 1253–1270
Snow AD, Mar H, Nochlin D, Kresse H, Wight TN (1992) Peripheral distribution of dermatan sulfate proteoglycans (decorin) in amyloid-containing plaques and their presence in neurofibrillary tangles of Alzheimer's Disease. J Histochem Cytochem 40: 105–113
Tabaton M, Cammarata S, Mancardi G, Manetto V, Autilio-Gambetti L, Perry G, Gambetti P (1991) Ultrastructural localization of β amyloid, τ, and ubiquitin epitopes in extracellular neurofibrillary tangles. Proc Natl Acad Sci USA 88: 2098–2102
Tago H, Kimura H, Maeda T (1986) Visualization of detailed acetylcholinesterase fiber and neuron staining in rat brain by a sensitive histochemical procedure. J Histochem Cytochem 34: 1431–1438
Watson RE Jr, Wiegand SJ, Clough RW, Hoffman CE (1986) Use of cryoprotectant to maintain long-term peptide immunoreactivity and tissue morphology. Peptides 7: 155–159
Wright CI, Geula C, Mesulam M-M (1993) Protease inhibitors and indoleamines selectively inhibit cholinesterases in the histopathologic structures of Alzheimer disease. Proc Natl Acad Sci USA 90: 683–686
Yamaguchi H, Nakazato Y, Shoji M, Ihara Y, Hirai S (1990) Ultrastructure of the neuropil threads in the Alzheimer brain: their dendritic origin and accumulation in the senile plaques. Acta Neuropathol 80: 368–374
Yen SH, Gaskin F, Fu SM (1983) Neurofibrillary tangles in senile dementia of the Alzheimer type share an antigenic determinant with intermediate filaments of the vimentin class. Am J Pathol 113: 373–381
Younkin SG, Goodridge B, Katz J, Lockett G, Nafziger D, Usiak MF, Younkin LH (1986) Molecular forms of acetylcholinesterases in Alzheimer's disease. Fed Proc 45: 2982–2988
Author information
Authors and Affiliations
Additional information
Supported by Fondo de Investigaciones Sanitarias de la Seguridad Social No. 93/0198, Spain
Rights and permissions
About this article
Cite this article
Morán, M.A., Mufson, E.J. & Gómez-Ramos, P. Cholinesterases colocalize with sites of neurofibrillary degeneration in aged and Alzheimer's brains. Acta Neuropathol 87, 284–292 (1994). https://doi.org/10.1007/BF00296744
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00296744