- Email: [email protected]
Morphologic difference of neuropil threads in Alzheimer's disease, corticobasal degeneration and progressive supranuclear palsy: a morphometric study
Neuroscience Letters 233 (1997) 89–92
Morphologic difference of neuropil threads in Alzheimer’s disease, corticobasal degeneration and progressive supranuclear palsy: a morphometric study Takashi Komori a ,*, Nobutaka Arai a, Masaya Oda b, Hiroshi Nakayama c, Shigeo Murayama d, Naoji Amano e, Noriyuki Shibata f, Makio Kobayashi f, Shoichi Sasaki g, Saburo Yagishita h a
Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu City, Tokyo 183, Japan b Department of Pathology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan c Department of Psychiatry, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan d Department of Neurology, University of Tokyo, Tokyo, Japan e Department of Psychiatry, University of Tokyo, Tokyo, Japan f Department of Pathology, Tokyo Women’s Medical College, Tokyo, Japan g Department of Neurology, Tokyo Women’s Medical College, Tokyo, Japan h Department of Pathology, Kanagawa Rehabilitation Center, Kanagawa, Japan Received 11 July 1997; received in revised form 15 August 1997; accepted 18 August 1997
Abstract Using Gallyas–Braak’s silver stain, neuropil threads (NTs) in Alzheimer’s disease (AD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) were analyzed morphologically and morphometrically. The NT density was highest in the cerebral cortical layer V in AD and CBD, and in the subcortical white matter in PSP. An overlaid, two-dimensional, camera lucida drawing revealed differences in the fine profile of NTs among these three disease groups. The differences were confirmed by computerized feature analysis which revealed differences in maximum length, breadth, Feret’s angle and orientation of the NTs. Unlike a previous assumption that all NTs have a similar appearance, our study revealed that NTs in AD, CBD and PSP were distinctively different with respect to their morphology. 1997 Elsevier Science Ireland Ltd. Keywords: Neuropil threads; Morphometry; Feature analysis; Alzheimer’s disease; Corticobasal degeneration; Progressive supranuclear palsy
Deposition of abnormally phosphorylated tau in the central nervous system is a major hallmark of neurodegenerative disorders [7]. Neuropil threads (NTs), scattered threadlike structures present mainly in the gray matter, are composed of hyper-phosphorylated tau within dystrophic cell processes [3]. NTs are detected at high sensitivity by silver impregnation methods, particularly by the use of Gallyas– Braak’s silver (GB) stain [6]. NTs are consistently found in the cerebral cortex of patients with Alzheimer’s disease (AD) [5], corticobasal degeneration (CBD) [10] and progressive supranuclear palsy (PSP) [9,10,12]. In AD, NTs * Corresponding author. Tel.: +81 423 258111; fax: +81 423 218678; e-mail: [email protected]
localize in the dendrites, but not in the axons or processes of glial cells [3,4]. In AD, the formation of NTs subsequently leads to the formation of extraneuronal neurofibrillary tangles (NFTs) and neuronal cell death [3]. Thus, NT formation is considered to be an early, important event in the AD process. For CBD and PSP, on the contrary, studies on cellular localization, morphologic characterization, and significance in the disease processes of NTs are limited and largely unsatisfactory. However, NTs have been considered to have a similar appearance in all types of neurodegenerative disorders [7]. In the present study, we investigated the morphologic and morphometric characteristics of NTs and their distribution in the cerebral cortical gyri in AD, CBD and PSP.
0304-3940/97/$17.00 1997 Elsevier Science Ireland Ltd. All rights reserved PII S0304- 3940 (97 )0 0635- 6
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T. Komori et al. / Neuroscience Letters 233 (1997) 89–92
Table 1 Fractional area density of neuropil threads at three different depths of the cerebral cortical gyrus Mean ± SD (%)
Layer III
Control AD CBD PSP
0.13 1.97 3.32 0.82
a
± ± ± ±
0.15 0.28** 0.37* 0.30**
Layer V 0.09 5.77 6.02 3.91
± ± ± ±
0.15 0.58** 1.25* 1.00**
Subcortical white matter 0.01 0.28 4.70 7.62
± ± ± ±
0.01 0.14** 0.02* 0.87**
ANOVA P-valuea .0.05 ,0.001 ,0.001 ,0.001
One-factor ANOVA. Statistically different compared to the other groups at *P , 0.05 and **P , 0.001 (Fisher’s least significant difference).
Five clinically and pathologically phenotypical cases, which met the proposed diagnostic criteria [14,15], for each of AD (average 82.4 years; range 68–90 years), CBD (average 72.0 years; range 65–82 years) and PSP (average 72.6 years; range 68–75 years) were selected for analysis. Five non-demented, aged individuals (average 86.2 years; range 85–90 years) served as controls. Ten per-
cent buffered-formalin-fixed, paraffin-embedded, 10 mm thick sections were obtained from multiple regions of brains. In addition to routine histochemical stainings, including hematoxylin and eosin staining, GB staining after pretreatment of sections with 0.3% KMnO4 was applied. For achievement of a consistent comparison between cases studied, analyses were targeted on the apex of
Fig. 1. The left column (a,d), AD brain; the middle column (b,e), CBD brain and the right column (c,f), PSP brain. (a–c) Middle-power photomicrographs of the cerebral cortex. (GB staining, (a) cortical layer III, (b) IV and (c) V; bars, 50 mm). (d–f) Overlaid two-dimensional, camera lucida drawings of NTs. Note the distinctive difference in profiles ((d–f) correspond to (a–c) respectively; bars, 5 mm).
91
T. Komori et al. / Neuroscience Letters 233 (1997) 89–92 Table 2 Feature analysis of neuropil threads Mean ± SD (n = 1000)
AD
Length (mm) Breadth (mm) Feret’s angle (v°) Orientation (v°)
6.02 2.27 55.8 85.4
a
CBD ± ± ± ±
4.55* 2.07 15.4** 39.3*
6.64 2.20 59.0 91.4
ANOVA P-valuea
PSP ± ± ± ±
4.77* 1.88 15.8** 35.3
12.3 3.89 62.3 88.9
± ± ± ±
10.1** 3.44** 15.9** 32.1**
,0.0001 ,0.0001 ,0.001 ,0.0001
One-factor ANOVA. Statistically different compared to the other groups at *P , 0.05 and **P , 0.001 (Fisher’s protected least significant difference).
the cerebral cortical gyrus, where NTs exhibited vertical arrangements. The inferior temporal gyrus for the control and AD subjects and the posterior superior frontal gyrus for CBD and PSP subjects were selected because these gyri showed the highest neocortical NT density compared to other areas examined (data not shown). Analyses were performed on the sections subjected to GB staining, using a computer-assisted image analysis system consisting of a microscope (Olympus BX 40), a CCD camera (KY-F55MD, Victor), a microcomputer (Power Macintosh 8500/120) and a software system (MacScope, Mitani Incorporated, Fukui, Japan). For one representative case from each disease group, a two-dimensional, camera lucida profile of GB-positive NTs was manually drawn from five overlaid, 2 mm interval step images of 10 mm thick sections. For morphometric analysis, the light microscopic images were inputted through the CCD camera, digitized as binary images and analyzed using the software system. In each case, the density of NTs was obtained in ten randomized fields at each of three different depths of the cortical gyrus: cortical layer III, V and subcortical white matter. Feature analysis was performed on 200 well-isolated NTs, which were manually identified on a monitor with a final magnification of 1900×, in individual cases, giving a total of 1000 in each disease group. Low-power photomicrographs of GB-stained sections of the cerebral gyrus in AD, CBD and PSP showed a laminar distribution of NTs (data not shown). Quantitatively, the fractional area density of these laminar NTs was high in the cerebral cortical layer V in AD (P , 0.001) and CBD (P , 0.05), while it was high in the subcortical white matter in PSP (P , 0.001) (Table 1). In addition, in AD, the NT density in the subcortical white matter was quite low (Table 1). In contrast, that of the control group was low overall (Table 1). In middle-power photomicrographs, abundant curved and irregular NTs were identified (Fig. 1a–c). The aggregation pattern, orientation and appearance of NTs were different in each disease group. These differences were most obvious in the overlaid, two-dimensional, camera lucida profile (Fig. 1d–f). In AD, fine NTs were distributed uniformly in the neuropil. In CBD, short, thick NTs aggregated and exhibited random orientation. In PSP, thick and winding NTs were arranged parallel to the direction of axonal bundles of the cortical gyrus. These differences in optical images were confirmed by quantitative analysis. Feature analysis on
NTs revealed significant differences in maximum length, breadth, Feret’s angle and orientation (P , 0.0001, onefactor ANOVA) between the three disease groups (Table 2). Feret’s angle is the angle of vertical and horizontal Feret’s diameters. Unlike a previous assumption that NTs in neurodegenerative disorders have a similar appearance, our study revealed that NTs exhibit distinctive distributional and morphologic differences among AD, CBD and PSP. We demonstrated that NTs in AD were found almost exclusively within the cerebral cortex. This result corresponds well with the fact that NTs in AD localize only in the dendrites of NFT-bearing neurons [4]. In contrast, we demonstrated that the density of NTs in PSP was the highest in the subcortical white matter where only axons are present. With respect to morphology, NTs in PSP were distinctively different from ‘dendritic’ NTs in AD. Our previous studies demonstrated that, histologically and ultrastructurally, NTs in the corticomedullary junctions of PSP were formed in the processes of oligodendrocytes [12,13]. A recent ultrastructural study also confirmed the presence of NTs in oligodendrocytic processes in the spinal gray matter [2]. Combined together, these data indicate that most NTs in PSP may be oligodendroglial but not neuronal in origin. Other distinctive differences found were in the distribution and morphology of NTs between CBD and PSP. These differences might be explained by differences in cellular localization or by as yet unidentified factors. The first possible factor is the difference in ultrastructural features; while 15 to 20 nm tubules with irregular constrictions were found in CBD, 13 to 15 nm tubules with fuzzy outer contours were found in PSP [1,2,10,16]. The second possibility is differences in tau which comprise NTs; an antibody against tau containing an alternatively spliced exon 3 did not recognize cytoskeletal lesions in CBD, but did in AD and PSP [8]. The third possible factor is cytoskeletal differences. Since GB staining detects not only abnormal tau but high-molecularweight microtubule-associated polypeptides (MAPs) [11], the morphologic differences in NTs upon GB staining may reflect differences in the basic subunit of MAPs rather than in tau. Although our study failed to provide information on basic cytoskeletal differences in NTs, the study should stimulate further investigation with more detailed morphologic characterization of NTs to understand their ultimate significance in the disease processes of AD, CBD and PSP.
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T. Komori et al. / Neuroscience Letters 233 (1997) 89–92
[1] Arima, K., Tubular profile of the Gallyas- and tau-positive argyrophilic threads in corticobasal degeneration: an electron microscopic study, Neuropathology, 16 (1996) 65–70. [2] Arima, K., Nakamura, M., Sunohara, N., Ogawa, M., Anno, M., Izumiyama, Y., Horai, S. and Ikeda, K., Ultrastructural characterization of the tau-immunoreactive tubules in the oligodendroglial perikarya and their inner loop processes in progressive supranuclear palsy, Acta Neuropathol., 93 (1997) 558–566. [3] Braak, E., Braak, H. and Mandelkow, E.M., A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads, Acta Neuropathol., 87 (1994) 554–567. [4] Braak, H. and Braak, E., Neuropil threads occur in dendrites of tangle-bearing nerve cells, Neuropathol. Appl. Neurobiol., 14 (1988) 39–44. [5] Braak, H., Braak, E., Grundke Iqbal, I. and Iqbal, K., Occurrence of neuropil threads in the senile human brain and in Alzheimer’s disease: a third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques, Neurosci. Lett., 65 (1986) 351– 355. [6] Braak, H., Braak, E., Ohm, T. and Bohl, J., Silver impregnation of Alzheimer’s neurofibrillary changes counterstained for basophilic material and lipofuscin pigment, Stain Technol., 63 (1988) 197–200. [7] Feany, M.B. and Dickson, D.W., Neurodegenerative disorders with extensive tau pathology: a comparative study and review, Ann. Neurol., 40 (1996) 139–148. [8] Feany, M.B., Ksiezakreding, H., Liu, W.K., Vincent, I., Yen, S.H.C. and Dickson, D.W., Epitope expression and hyperphosphorylation of tau protein in corticobasal degeneration – differentiation from progressive supranuclear palsy, Acta Neuropathol., 90 (1995) 37–43. [9] Hauw, J.J., Verny, M., Delaere, P., Cervera, P., He, Y. and Duyckaerts, C., Constant neurofibrillary changes in the neocortex
[10]
[11]
[12]
[13]
[14]
[15]
[16]
in progressive supranuclear palsy. Basic differences with Alzheimer’s disease and aging, Neurosci. Lett., 119 (1990) 182–186. Ikeda, K., Akiyama, H., Haga, C., Kondo, H., Arima, K. and Oda, T., Argyrophilic thread-like structure in corticobasal degeneration and supranuclear palsy, Neurosci. Lett., 174 (1994) 157–159. Iqbal, K., Braak, E., Braak, H., Zaidi, T. and Grundke Iqbal, I., A silver impregnation method for labeling both Alzheimer paired helical filaments and their polypeptides separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Neurobiol. Aging, 12 (1991) 357–361. Komori, T., Shibata, N., Kobayashi, M. and Sasaki, S., Argyrophilic meshwork structures in the cerebral cortex of patients with progressive supranuclear palsy, Neuropathology, 16 (1995) 1–5. Komori, T., Shibata, N., Kobayashi, M., Sasaki, S. and Iwata, M., Cerebral cortical abnormality in patients with progressive supranuclear palsy: a pathological study, Neurobiol. Aging, 17 (1996) 69. Litvan, I., Hauw, J.J., Bartko, J.J., Lantos, P.L., Daniel, S.E., Horoupian, D.S., McKee, A., Dickson, D., Bancher, C., Tabaton, M., Jellinger, K. and Anderson, D.W., Validity and reliability of the preliminary NINDS neuropathologic criteria for progressive supranuclear palsy and related disorders, J. Neuropathol. Exp. Neurol., 55 (1996) 97–105. Mirra, S.S., Heyman, A., McKeel, D., Sumi, S.M., Crain, B.J., Brownlee, L.M., Vogel, F.S., Hughes, J.P., van Belle, G. and Berg, L., The consortium to establish a registry for Alzheimer’s disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease, Neurology, 41 (1991) 479–486. Wakabayashi, K., Oyanagi, K., Makifuchi, T., Ikuta, F., Homma, A., Homma, Y., Horikawa, Y. and Tokiguchi, S., Corticobasal degeneration: etiopathological significance of the cytoskeletal alterations, Acta Neuropathol., 87 (1994) 545–553.
Morphologic difference of neuropil threads in Alzheimer’s disease, corticobasal degeneration and progressive supranuclear palsy: a morphometric study Takashi Komori a ,*, Nobutaka Arai a, Masaya Oda b, Hiroshi Nakayama c, Shigeo Murayama d, Naoji Amano e, Noriyuki Shibata f, Makio Kobayashi f, Shoichi Sasaki g, Saburo Yagishita h a
Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu City, Tokyo 183, Japan b Department of Pathology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan c Department of Psychiatry, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan d Department of Neurology, University of Tokyo, Tokyo, Japan e Department of Psychiatry, University of Tokyo, Tokyo, Japan f Department of Pathology, Tokyo Women’s Medical College, Tokyo, Japan g Department of Neurology, Tokyo Women’s Medical College, Tokyo, Japan h Department of Pathology, Kanagawa Rehabilitation Center, Kanagawa, Japan Received 11 July 1997; received in revised form 15 August 1997; accepted 18 August 1997
Abstract Using Gallyas–Braak’s silver stain, neuropil threads (NTs) in Alzheimer’s disease (AD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) were analyzed morphologically and morphometrically. The NT density was highest in the cerebral cortical layer V in AD and CBD, and in the subcortical white matter in PSP. An overlaid, two-dimensional, camera lucida drawing revealed differences in the fine profile of NTs among these three disease groups. The differences were confirmed by computerized feature analysis which revealed differences in maximum length, breadth, Feret’s angle and orientation of the NTs. Unlike a previous assumption that all NTs have a similar appearance, our study revealed that NTs in AD, CBD and PSP were distinctively different with respect to their morphology. 1997 Elsevier Science Ireland Ltd. Keywords: Neuropil threads; Morphometry; Feature analysis; Alzheimer’s disease; Corticobasal degeneration; Progressive supranuclear palsy
Deposition of abnormally phosphorylated tau in the central nervous system is a major hallmark of neurodegenerative disorders [7]. Neuropil threads (NTs), scattered threadlike structures present mainly in the gray matter, are composed of hyper-phosphorylated tau within dystrophic cell processes [3]. NTs are detected at high sensitivity by silver impregnation methods, particularly by the use of Gallyas– Braak’s silver (GB) stain [6]. NTs are consistently found in the cerebral cortex of patients with Alzheimer’s disease (AD) [5], corticobasal degeneration (CBD) [10] and progressive supranuclear palsy (PSP) [9,10,12]. In AD, NTs * Corresponding author. Tel.: +81 423 258111; fax: +81 423 218678; e-mail: [email protected]
localize in the dendrites, but not in the axons or processes of glial cells [3,4]. In AD, the formation of NTs subsequently leads to the formation of extraneuronal neurofibrillary tangles (NFTs) and neuronal cell death [3]. Thus, NT formation is considered to be an early, important event in the AD process. For CBD and PSP, on the contrary, studies on cellular localization, morphologic characterization, and significance in the disease processes of NTs are limited and largely unsatisfactory. However, NTs have been considered to have a similar appearance in all types of neurodegenerative disorders [7]. In the present study, we investigated the morphologic and morphometric characteristics of NTs and their distribution in the cerebral cortical gyri in AD, CBD and PSP.
0304-3940/97/$17.00 1997 Elsevier Science Ireland Ltd. All rights reserved PII S0304- 3940 (97 )0 0635- 6
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T. Komori et al. / Neuroscience Letters 233 (1997) 89–92
Table 1 Fractional area density of neuropil threads at three different depths of the cerebral cortical gyrus Mean ± SD (%)
Layer III
Control AD CBD PSP
0.13 1.97 3.32 0.82
a
± ± ± ±
0.15 0.28** 0.37* 0.30**
Layer V 0.09 5.77 6.02 3.91
± ± ± ±
0.15 0.58** 1.25* 1.00**
Subcortical white matter 0.01 0.28 4.70 7.62
± ± ± ±
0.01 0.14** 0.02* 0.87**
ANOVA P-valuea .0.05 ,0.001 ,0.001 ,0.001
One-factor ANOVA. Statistically different compared to the other groups at *P , 0.05 and **P , 0.001 (Fisher’s least significant difference).
Five clinically and pathologically phenotypical cases, which met the proposed diagnostic criteria [14,15], for each of AD (average 82.4 years; range 68–90 years), CBD (average 72.0 years; range 65–82 years) and PSP (average 72.6 years; range 68–75 years) were selected for analysis. Five non-demented, aged individuals (average 86.2 years; range 85–90 years) served as controls. Ten per-
cent buffered-formalin-fixed, paraffin-embedded, 10 mm thick sections were obtained from multiple regions of brains. In addition to routine histochemical stainings, including hematoxylin and eosin staining, GB staining after pretreatment of sections with 0.3% KMnO4 was applied. For achievement of a consistent comparison between cases studied, analyses were targeted on the apex of
Fig. 1. The left column (a,d), AD brain; the middle column (b,e), CBD brain and the right column (c,f), PSP brain. (a–c) Middle-power photomicrographs of the cerebral cortex. (GB staining, (a) cortical layer III, (b) IV and (c) V; bars, 50 mm). (d–f) Overlaid two-dimensional, camera lucida drawings of NTs. Note the distinctive difference in profiles ((d–f) correspond to (a–c) respectively; bars, 5 mm).
91
T. Komori et al. / Neuroscience Letters 233 (1997) 89–92 Table 2 Feature analysis of neuropil threads Mean ± SD (n = 1000)
AD
Length (mm) Breadth (mm) Feret’s angle (v°) Orientation (v°)
6.02 2.27 55.8 85.4
a
CBD ± ± ± ±
4.55* 2.07 15.4** 39.3*
6.64 2.20 59.0 91.4
ANOVA P-valuea
PSP ± ± ± ±
4.77* 1.88 15.8** 35.3
12.3 3.89 62.3 88.9
± ± ± ±
10.1** 3.44** 15.9** 32.1**
,0.0001 ,0.0001 ,0.001 ,0.0001
One-factor ANOVA. Statistically different compared to the other groups at *P , 0.05 and **P , 0.001 (Fisher’s protected least significant difference).
the cerebral cortical gyrus, where NTs exhibited vertical arrangements. The inferior temporal gyrus for the control and AD subjects and the posterior superior frontal gyrus for CBD and PSP subjects were selected because these gyri showed the highest neocortical NT density compared to other areas examined (data not shown). Analyses were performed on the sections subjected to GB staining, using a computer-assisted image analysis system consisting of a microscope (Olympus BX 40), a CCD camera (KY-F55MD, Victor), a microcomputer (Power Macintosh 8500/120) and a software system (MacScope, Mitani Incorporated, Fukui, Japan). For one representative case from each disease group, a two-dimensional, camera lucida profile of GB-positive NTs was manually drawn from five overlaid, 2 mm interval step images of 10 mm thick sections. For morphometric analysis, the light microscopic images were inputted through the CCD camera, digitized as binary images and analyzed using the software system. In each case, the density of NTs was obtained in ten randomized fields at each of three different depths of the cortical gyrus: cortical layer III, V and subcortical white matter. Feature analysis was performed on 200 well-isolated NTs, which were manually identified on a monitor with a final magnification of 1900×, in individual cases, giving a total of 1000 in each disease group. Low-power photomicrographs of GB-stained sections of the cerebral gyrus in AD, CBD and PSP showed a laminar distribution of NTs (data not shown). Quantitatively, the fractional area density of these laminar NTs was high in the cerebral cortical layer V in AD (P , 0.001) and CBD (P , 0.05), while it was high in the subcortical white matter in PSP (P , 0.001) (Table 1). In addition, in AD, the NT density in the subcortical white matter was quite low (Table 1). In contrast, that of the control group was low overall (Table 1). In middle-power photomicrographs, abundant curved and irregular NTs were identified (Fig. 1a–c). The aggregation pattern, orientation and appearance of NTs were different in each disease group. These differences were most obvious in the overlaid, two-dimensional, camera lucida profile (Fig. 1d–f). In AD, fine NTs were distributed uniformly in the neuropil. In CBD, short, thick NTs aggregated and exhibited random orientation. In PSP, thick and winding NTs were arranged parallel to the direction of axonal bundles of the cortical gyrus. These differences in optical images were confirmed by quantitative analysis. Feature analysis on
NTs revealed significant differences in maximum length, breadth, Feret’s angle and orientation (P , 0.0001, onefactor ANOVA) between the three disease groups (Table 2). Feret’s angle is the angle of vertical and horizontal Feret’s diameters. Unlike a previous assumption that NTs in neurodegenerative disorders have a similar appearance, our study revealed that NTs exhibit distinctive distributional and morphologic differences among AD, CBD and PSP. We demonstrated that NTs in AD were found almost exclusively within the cerebral cortex. This result corresponds well with the fact that NTs in AD localize only in the dendrites of NFT-bearing neurons [4]. In contrast, we demonstrated that the density of NTs in PSP was the highest in the subcortical white matter where only axons are present. With respect to morphology, NTs in PSP were distinctively different from ‘dendritic’ NTs in AD. Our previous studies demonstrated that, histologically and ultrastructurally, NTs in the corticomedullary junctions of PSP were formed in the processes of oligodendrocytes [12,13]. A recent ultrastructural study also confirmed the presence of NTs in oligodendrocytic processes in the spinal gray matter [2]. Combined together, these data indicate that most NTs in PSP may be oligodendroglial but not neuronal in origin. Other distinctive differences found were in the distribution and morphology of NTs between CBD and PSP. These differences might be explained by differences in cellular localization or by as yet unidentified factors. The first possible factor is the difference in ultrastructural features; while 15 to 20 nm tubules with irregular constrictions were found in CBD, 13 to 15 nm tubules with fuzzy outer contours were found in PSP [1,2,10,16]. The second possibility is differences in tau which comprise NTs; an antibody against tau containing an alternatively spliced exon 3 did not recognize cytoskeletal lesions in CBD, but did in AD and PSP [8]. The third possible factor is cytoskeletal differences. Since GB staining detects not only abnormal tau but high-molecularweight microtubule-associated polypeptides (MAPs) [11], the morphologic differences in NTs upon GB staining may reflect differences in the basic subunit of MAPs rather than in tau. Although our study failed to provide information on basic cytoskeletal differences in NTs, the study should stimulate further investigation with more detailed morphologic characterization of NTs to understand their ultimate significance in the disease processes of AD, CBD and PSP.
92
T. Komori et al. / Neuroscience Letters 233 (1997) 89–92
[1] Arima, K., Tubular profile of the Gallyas- and tau-positive argyrophilic threads in corticobasal degeneration: an electron microscopic study, Neuropathology, 16 (1996) 65–70. [2] Arima, K., Nakamura, M., Sunohara, N., Ogawa, M., Anno, M., Izumiyama, Y., Horai, S. and Ikeda, K., Ultrastructural characterization of the tau-immunoreactive tubules in the oligodendroglial perikarya and their inner loop processes in progressive supranuclear palsy, Acta Neuropathol., 93 (1997) 558–566. [3] Braak, E., Braak, H. and Mandelkow, E.M., A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads, Acta Neuropathol., 87 (1994) 554–567. [4] Braak, H. and Braak, E., Neuropil threads occur in dendrites of tangle-bearing nerve cells, Neuropathol. Appl. Neurobiol., 14 (1988) 39–44. [5] Braak, H., Braak, E., Grundke Iqbal, I. and Iqbal, K., Occurrence of neuropil threads in the senile human brain and in Alzheimer’s disease: a third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques, Neurosci. Lett., 65 (1986) 351– 355. [6] Braak, H., Braak, E., Ohm, T. and Bohl, J., Silver impregnation of Alzheimer’s neurofibrillary changes counterstained for basophilic material and lipofuscin pigment, Stain Technol., 63 (1988) 197–200. [7] Feany, M.B. and Dickson, D.W., Neurodegenerative disorders with extensive tau pathology: a comparative study and review, Ann. Neurol., 40 (1996) 139–148. [8] Feany, M.B., Ksiezakreding, H., Liu, W.K., Vincent, I., Yen, S.H.C. and Dickson, D.W., Epitope expression and hyperphosphorylation of tau protein in corticobasal degeneration – differentiation from progressive supranuclear palsy, Acta Neuropathol., 90 (1995) 37–43. [9] Hauw, J.J., Verny, M., Delaere, P., Cervera, P., He, Y. and Duyckaerts, C., Constant neurofibrillary changes in the neocortex
[10]
[11]
[12]
[13]
[14]
[15]
[16]
in progressive supranuclear palsy. Basic differences with Alzheimer’s disease and aging, Neurosci. Lett., 119 (1990) 182–186. Ikeda, K., Akiyama, H., Haga, C., Kondo, H., Arima, K. and Oda, T., Argyrophilic thread-like structure in corticobasal degeneration and supranuclear palsy, Neurosci. Lett., 174 (1994) 157–159. Iqbal, K., Braak, E., Braak, H., Zaidi, T. and Grundke Iqbal, I., A silver impregnation method for labeling both Alzheimer paired helical filaments and their polypeptides separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Neurobiol. Aging, 12 (1991) 357–361. Komori, T., Shibata, N., Kobayashi, M. and Sasaki, S., Argyrophilic meshwork structures in the cerebral cortex of patients with progressive supranuclear palsy, Neuropathology, 16 (1995) 1–5. Komori, T., Shibata, N., Kobayashi, M., Sasaki, S. and Iwata, M., Cerebral cortical abnormality in patients with progressive supranuclear palsy: a pathological study, Neurobiol. Aging, 17 (1996) 69. Litvan, I., Hauw, J.J., Bartko, J.J., Lantos, P.L., Daniel, S.E., Horoupian, D.S., McKee, A., Dickson, D., Bancher, C., Tabaton, M., Jellinger, K. and Anderson, D.W., Validity and reliability of the preliminary NINDS neuropathologic criteria for progressive supranuclear palsy and related disorders, J. Neuropathol. Exp. Neurol., 55 (1996) 97–105. Mirra, S.S., Heyman, A., McKeel, D., Sumi, S.M., Crain, B.J., Brownlee, L.M., Vogel, F.S., Hughes, J.P., van Belle, G. and Berg, L., The consortium to establish a registry for Alzheimer’s disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease, Neurology, 41 (1991) 479–486. Wakabayashi, K., Oyanagi, K., Makifuchi, T., Ikuta, F., Homma, A., Homma, Y., Horikawa, Y. and Tokiguchi, S., Corticobasal degeneration: etiopathological significance of the cytoskeletal alterations, Acta Neuropathol., 87 (1994) 545–553.