Top

Published in:

01-05-2011 | Dementias - Original Article

TAR-DNA binding protein-43 and alterations in the hippocampus

Authors: Tuomas Rauramaa, Maria Pikkarainen, Elisabet Englund, Paul G. Ince, Kurt Jellinger, Anders Paetau, Irina Alafuzoff

Published in: Journal of Neural Transmission | Issue 5/2011

Abstract

Immunocytochemistry for transactive response binding protein-43 (TDP43) was assessed in the granular cell layer of the dentate gyrus in 250 cases displaying hippocampal pathology identified by haematoxylin–eosin staining. 18%, nearly one in five displayed TDP43 immunoreactive pathology in the granular cell layer of hippocampus. This percentage increased to 43% when only subjects with hippocampal pathology other than vascular in origin were included. When only subjects with severe Alzheimer’s disease-related pathology were included, 42% displayed TDP43-immunoreactive pathology, increasing to 60% when concomitant Alzheimer’s disease and α-synuclein pathology were present. Within this setting, TDP43-immunoreactive pathology was observed to be present in 6% of subjects with hippocampal pathology but without any cognitive impairment. Our findings justify assessment of TDP43 pathology in every case where a pathological alteration is observed in the hippocampus using a routine stain.

Alafuzoff I, Helisalmi S, Mannermaa A, Riekkinen P Sr, Soininen H (1999) Beta-amyloid load is not influenced by the severity of cardiovascular disease in aged and demented patients. Stroke 30:613–618

Alafuzoff I, Arzberger T, Al-Sarraj S et al (2008) Staging of neurofibrillary pathology in Alzheimer’s disease: a study of the BrainNet Europe Consortium. Brain Pathol 18:484–496PubMed

Alafuzoff I, Thal DR, Arzberger T et al (2009a) Assessment of β-amyloid deposits in human brain: a study of the BrainNet Europe Consortium. Acta Neuropathol 117:309–320PubMedCrossRef

Alafuzoff I, Ince PG, Arzberger T et al (2009b) Staging/typing of Lewy body related alpha-synuclein pathology: a study of the BrainNet Europe Consortium. Acta Neuropathol 117:635–652PubMedCrossRef

Amador-Ortiz C, Lin WL, Ahmed Z et al (2007) TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer’s disease. Ann Neurol 61:435–445PubMedCrossRef

Arai T, Hasegawa M, Akiyama H et al (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 351:602–611PubMedCrossRef

Arai T, Mackenzie IR, Hasegawa M et al (2009) Phosphorylated TDP-43 in Alzheimer’s disease and dementia with Lewy bodies. Acta Neuropathol 117:125–136PubMedCrossRef

Braak H, Alafuzoff I, Arzberger T et al (2006) Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol 112:389–404PubMedCrossRef

Chen-Plotkin AS, Lee VM, Trojanowski JQ (2010) TAR DNA-binding protein 43 in neurodegenerative disease. Nat Rev Neurol 6(4):211–220PubMedCrossRef

Freeman SH, Spires-Jones T, Hyman BT et al (2008) TAR-DNA binding protein 43 in Pick disease. J Neuropathol Exp Neurol 67:62–67PubMedCrossRef

Fujishiro H, Uchikado H, Arai T et al (2009) Accumulation of phosphorylated TDP-43 in brains of patients with argyrophilic grain disease. Acta Neuropathol 117:151–158PubMedCrossRef

Geser F, Lee VM, Trojanowski JQ (2010) Amyotrophic lateral sclerosis and frontotemporal lobar degeneration: a spectrum of TDP-43 proteinopathies. Neuropathology 30(2):103–112PubMedCrossRef

Hatanpää KJ, Bigio EH, Cairns NJ et al (2008) TAR DNA-binding protein 43 immunohistochemistry reveals extensive neuritic pathology in FTLD-U: a midwest-southwest consortium for FTLD study. J Neuropathol Exp Neurol 67:271–279PubMedCrossRef

Higashi S, Iseki E, Yamamoto R et al (2007) Concurrence of TDP-43, tau and alpha-synuclein pathology in brains of Alzheimer’s disease and dementia with Lewy bodies. Brain Res 1184:284–294PubMedCrossRef

Hu WT, Josephs KA, Knopman DS et al (2008) Temporal lobar predominance of TDP-43 neuronal cytoplasmic inclusions in Alzheimer disease. Acta Neuropathol 116:215–220PubMedCrossRef

Josephs KA, Holton JL, Rossor MN et al (2004) Frontotemporal lobar degeneration and ubiquitin immunohistochemistry. Neuropathol Appl Neurobiol 30:369–373PubMedCrossRef

Josephs KA, Whitwell JL, Knopman DS et al (2008) Abnormal TDP-43 immunoreactivity in AD modifies clinicopathologic and radiologic phenotype. Neurology 70:1850–1857PubMedCrossRef

Kadokura A, Yamazaki T, Lemere CA et al (2009) Regional distribution of TDP-43 inclusions in Alzheimer disease (AD) brains: their relation to AD common pathology. Neuropathology 29:566–573PubMedCrossRef

Kuusisto E, Parkkinen L, Alafuzoff I (2003) Morphogenesis of Lewy bodies: dissimilar incorporation of alpha-synuclein, ubiquitin, and p62. J Neuropathol Exp Neurol 62:1241–1253PubMed

Kuusisto E, Kauppinen T, Alafuzoff I (2008) Use of p62/SQSTM1 antibodies for neuropathological diagnosis. Neuropathol Appl Neurobiol 34:169–180PubMedCrossRef

Mackenzie IR, Neumann M, Bigio EH et al (2010) Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update. Acta Neuropathol 119:1–4PubMedCrossRef

Mateen FJ, Josephs KA (2009) TDP-43 is not present in brain tissue of patients with schizophrenia. Schizophr Res 108:297–298PubMedCrossRef

McKhann G, Drachman D, Folstein M et al (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–944PubMed

Nakashima-Yasuda H, Uryu K, Robinson J et al (2007) Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases. Acta Neuropathol 114:221–229PubMedCrossRef

Nelson PT, Abner EL, Schmitt FA et al (2010) Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons. Brain Pathol 20:66–79PubMedCrossRef

Neumann M, Sampathu DM, Kwong LK et al (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130–133PubMedCrossRef

Parkkinen L, Soininen H, Laakso M et al (2001) Alpha-synuclein pathology is highly dependent on the case selection. Neuropathol Appl Neurobiol 27:314–325PubMedCrossRef

Paulson HL (2009) The spinocerebellar ataxias. J Neuroophthalmol 29:227–237PubMed

Tolnay M, Clavaguera F (2004) Argyrophilic grain disease: a late-onset dementia with distinctive features among tauopathies. Neuropathology 24:269–283PubMedCrossRef

Uryu K, Nakashima-Yasuda H, Forman MS et al (2008) Concomitant TAR-DNA-binding protein 43 pathology is present in Alzheimer disease and corticobasal degeneration but not in other tauopathies. J Neuropathol Exp Neurol 67:555–564PubMedCrossRef

Wang HY, Wang IF, Bose J, Shen CK (2004) Structural diversity and functional implications of the eukaryotic TDP gene family. Genomics 83:130–139PubMedCrossRef

Williams DR, Lees AJ (2009) Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges. Lancet Neurol 8:270–279PubMedCrossRef

Title: TAR-DNA binding protein-43 and alterations in the hippocampus
Authors: Tuomas Rauramaa
Maria Pikkarainen
Elisabet Englund
Paul G. Ince
Kurt Jellinger
Anders Paetau
Irina Alafuzoff
Publication date: 01-05-2011
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 5/2011
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-010-0574-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

TAR-DNA binding protein-43 and alterations in the hippocampus

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2011

Cerebral amyloid angiopathy in streptozotocin rat model of sporadic Alzheimer’s disease: a long-term follow up study

Prospective study on association between plasma amyloid beta-42 and atherosclerotic risk factors

Fronto-temporal lobar degeneration: neuropathology in 60 cases

Prof. Dr. Kurt Jellinger: an appreciation on the occasion of his anniversary

Reduced secretagogin expression in the hippocampus of P301L tau transgenic mice

Modelling progressive autonomic failure in MSA: where are we now?