Comparison of the neurofibrillary pathology in Alzheimer’s disease and familial presenile dementia with tangles
Abstract
Alzheimer's disease (AD) is characterised neuropathologically by the presence of abundant extracellular beta-amyloid deposits and intracellular neurofibrillary lesions consisting of neurofibrillary tangles, neuropil threads and senile plaque neurites which contain paired helical filaments (PHFs) made of hyperphosphorylated microtubule-associated protein tau. A new familial form of presenile dementia with neurofibrillary pathology and no beta-amyloid deposits has been described recently [Sumi et al. (1992) Neurology 42: 120-127]. We have compared the tau pathology in this familial form of presenile dementia with that of AD. To this end we have used electron microscopy, immunoblotting and immunohistochemistry with phosphorylation-dependent (PHF1, AT8, AT100, AT180, AT270, 12E8) and phosphorylation-independent (BR133, BR134) anti-tau antibodies. We show that in the two diseases dispersed PHFs are structurally, biochemically and immunologically identical; they are stained by all anti-tau antibodies used and on immunoblots PHF-tau appears as three major bands of 60, 64 and 68 kDa. However, while the anti-tau antibodies stain neurofibrillary tangles, neuropil threads and neuritic plaques in AD brain, no neuritic plaques are found in familial presenile dementia. These results indicate that in the two diseases tau undergoes the same modifications; they confirm that neurofibrillary tangles and neuropil threads like those in AD can exist independently of beta-amyloid deposits and that…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The tau-V337M mutation is located in MAPT exon 12, expressed in iPSC-derived neurons, and associated with FTD with abundant neurofibrillary tangles in frontal and temporal cortices and the cingulate gyrus and atrophy throughout the hippocampus and amygdala.
“The tau-V337M mutation selected for this study is located in MAPT exon 12, expressed in iPSC-derived neurons, and associated with FTD with abundant neurofibrillary tangles in frontal and temporal cortices and the cingulate gyrus and atrophy throughout the hippocampus and amygdala (Spillantini et al., 1996; Spina et al., 2017; Sumi et al., 1992).”
From ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids (2021) · cites this paper as Spillantini et al., 1996
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., & Hyman, B. T. (1992) · Neurology · doi:10.1212/wnl.42.3.631 · Cited by 2,668 · see citing works
A68: a Major Subunit of Paired Helical Filaments and Derivatized Forms of Normal Tau
Lee, V. M.-Y., Balin, B. J., Otvos, L., & Trojanowski, J. Q. (1991) · Science · doi:10.1126/science.1899488 · Cited by 1,418 · see citing works
Monoclonal antibody AT8 recognises tau protein phosphorylated at both serine 202 and threonine 205
Goedert, M., Jakes, R., & Vanmechelen, E. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11484-e · Cited by 608 · see citing works
Self-citationMonoclonal antibody PHF‐1 recognizes tau protein phosphorylated at serine residues 396 and 404
Otvos, L., Feiner, L., Lang, E., Szendrei, G. I., Goedert, M., & Lee, V. M. (1994) · Journal of Neuroscience Research · doi:10.1002/jnr.490390607 · Cited by 488 · cited 1× · see citing works
“AT8 recognises tau phosphorylated at Ser 202 and Thr 205 (in the numbering of the longest human brain tau isoform, [23]) [25, 27], AT270 recognises tau phosphorylated at Thr 181 [26], AT180 recognises tau phosphorylated at Thr 231 and Ser 235 [40], PHF1 recognises tau phosphorylated at Ser 396 and Ser 404 [ 45 ], 12E8…”
BackgroundSelf-citationGoedert, M., Jakes, R., Crowther, R. A., Cohen, P., Vanmechelen, E., Vandermeeren, M., & Cras, P. (1994) · Biochemical Journal · doi:10.1042/bj3010871 · Cited by 375 · see citing works
Self-citationDelaère, P., Duyckaerts, C., Masters, C., Beyreuther, K., Piette, F., & Hauw, J.-J. (1990) · Neuroscience Letters · doi:10.1016/0304-3940(90)90391-l · Cited by 186 · see citing works
Pathological markers associated with normal aging and dementia in the elderly
Crystal, H. A., Dickson, D. W., Sliwinski, M. J., Lipton, R. B., Grober, E., Marks‐Nelson, H., & Antis, P. (1993) · Annals of Neurology · doi:10.1002/ana.410340410 · Cited by 161 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Lee, V. M.-Y., Goedert, M., & Trojanowski, J. Q. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1121 · Cited by 2,480 · see citing works
Self-citationMutation in the tau gene in familial multiple system tauopathy with presenile dementia
Spillantini, M. G., Murrell, J. R., Goedert, M., Farlow, M. R., Klug, A., & Ghetti, B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7737 · Cited by 1,474 · see citing works
Self-citationTau is a candidate gene for chromosome 17 frontotemporal dementia
Poorkaj, P., Bird, T. D., Wijsman, E., Nemens, E., Garruto, R. M., Anderson, L., Andreadis, A., Wiederholt, W. C., Raskind, M., & Schellenberg, G. D. (1998) · Annals of Neurology · doi:10.1002/ana.410430617 · Cited by 1,374 · see citing works
Arendt, T., Stieler, J. T., & Holzer, M. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.08.018 · Cited by 609 · see citing works
The Unfolded Protein Response Is Activated in Pretangle Neurons in Alzheimer's Disease Hippocampus
Hoozemans, J. J. M., van Haastert, E. S., Nijholt, D. A. T., Rozemuller, A. J. M., Eikelenboom, P., & Scheper, W. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.080814 · Cited by 600 · see citing works
Neuronal cytoskeletal changes are an early consequence of repetitive head injury
Geddes, J. F., Vowles, G. H., Nicoll, J. A. R., & Révész, T. (1999) · Acta Neuropathologica · doi:10.1007/s004010051066 · Cited by 323 · see citing works
Tau Mutations Cause Frontotemporal Dementias
Goedert, M., Crowther, R. A., & Spillantini, M. G. (1998) · Neuron · doi:10.1016/s0896-6273(00)80615-7 · Cited by 268 · see citing works
Self-citationBowles, K. R., Silva, M. C., Whitney, K., Bertucci, T., Berlind, J. E., Lai, J. D., Garza, J. C., Boles, N. C., Mahali, S., Strang, K. H., et al. (2021) · Cell · doi:10.1016/j.cell.2021.07.003 · Cited by 175 · see citing works
A comprehensive resource for induced pluripotent stem cells from patients with primary tauopathies
Karch, C. M., Kao, A. W., Karydas, A., Onanuga, K., Martinez, R., Argouarch, A., Wang, C., Huang, C., Sohn, P. D., Bowles, K. R., et al. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.09.006 · Cited by 119 · see citing works
Han, D., Qureshi, H. Y., Lu, Y., & Paudel, H. K. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m901095200 · Cited by 40 · see citing works
Josephs, K. A. (2018) · Brain · doi:10.1093/brain/awx367 · Cited by 17 · see citing works
- Authors
- Spillantini, M. G., Crowther, R. A., & Goedert, M.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Venue
- Acta Neuropathologica
- Published
- 1996-06-17
- Volume
- 92
- Issue
- 1
- Pages
- 42-48
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2064494790
- Cited by
- 160
- References
- 8
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 2 · 2022: 2 · 2021: 8 · 2020: 5 · 2019: 4 · 2018: 3 · 2017: 7 · 2016: 4 · 2015: 3 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 8.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centre National de la Recherche Scientifique
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, neurofibrillary tangles, neuropil threads, paired helical filaments, tau hyperphosphorylation, tau pathology, amyloid-beta, anti-tau antibodies, PHF1, AT8, amyloid plaques, neuritic plaques
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Dementia, Humans, Immunohistochemistry, Immunoblotting, Neurofibrillary Tangles, tau Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
