Specific anti-beta tubulin antibodies in differential diagnosis of dementias
Authors:
D. Škoda 1; J. Hort 1; M. Vyhnálek 1; L. Glosová 1; M. Mináriková 1; P. Jinoch 2; K. Kranda 3; M. Bojar 1
Authors place of work:
Neurologická klinika, 2. LF UK a FN Motol, Praha
1; VIDIA s. r. o., Jesenice u Prahy
2; Charité Universitätsmedizin, Berlin
3
Published in the journal:
Cesk Slov Neurol N 2007; 70/103(2): 152-157
Category:
Original Paper
Summary
The aim:
To elucidate whether primarily atrophic degenerative affection can be differentiated from the affection of vascular origin by examining antibodies against fragments of the neuronal cytoskeleton in patients with dementia.
Methods:
A set of 37 patients with a syndrome of dementia involved 8 patients with Alzheimer´s disease (AD), 8 patients with frontotemporal lobar degeneration (FTLD), 11 patients with vascular dementia (VD), and 10 patients with mixed dementia (MD). A control set consisted of 10 subjects without disturbed cognitive functions. The diagnosis was established by means of basic clinical examinations, evaluations of MRI and of laboratory methods (determination of phospho-tau protein, tau protein, beta-amyloid in the cerebrospinal fluid). The serums and cerebrospinal fluids (CSF) of these patients were examined using ELISA method for the presence of specific antibodies against the neuronal cytoskeleton, microtubular subunit – beta-tubulin (btcIII).
Results:
In the sets of patients with dementia the levels of IgM antibodies both in CSF and serum did not differ statistically significantly from those in the controls. Positive titres of IgG anti-btcIII antibodies in CSF were shown in 56% patients with VD, in 33% patients with MD, and in 25% patients with FTLD. Positive titres of IgG antibodies against btcIII in serum were revealed in 40% patients with MD, in 36% patients with VD, and in 13% patients with FTLD. No positive result of IgG antibodies in serum as well as in CSF was recorded in a set of patients with AD and in controls.
Conclusion:
Positive titres of antibodies of IgG class against btcIII in serum and CSF were detected in patients with VD and MD in contrast to patients with AD. After verifying the results in a larger set of subjects, the examination of these specific antibodies can make the differential diagnosis of AD, MD and VD more accurate.
Key words:
Alzheimer´s disease, anti-btcIII antibodies, apoptosis, frontotemporal lobar degeneration, markers of dementia, necrosis, mixed dementia, vascular dementia.
Zdroje
1. Hedden T, Gabrieli JD. Healthy and pathological processes in adult development: new evidence from neuroimaging of the aging brain. Curr Opin Neurol 2005; 18: 740-7.
2. Glosová L, Hort J, Bojar M, Škoda D. Vyšetření celkového tau proteinu, phospho-tau proteinu a beta-amyloidu v mozkomíšním moku – naše první zkušenosti. Klin Biochem Metabol 2003; 12: 113-6.
3. Andreasen N, Sjogren M, Blennow K. CSF markers for Alzheimer´s disease: total tau, phospho-tau a Abeta42. World J Biol Psychiatry 2003; 4: 147-55.
4. Blennow K. Cerebrospinal fluid protein biomarkers for Alzheimer's disease. NeuroRx 2004; 1: 213-25.
5. Neary D, Snowden J, Mann D. Frontotemporal dementia. Lancet Neurol 2005; 4: 771-80.
6. Sullivan KF, Cleveland DW. Identification of conserved isotype-defining variable region sequences for four vertebrate beta tubulin polypeptide classes. Proc Natl Acad Sci USA 1986; 83: 4327-31.
7. Banerjee A, Roach MC, Trcka P, Luduena RF. Increased microtubule assembly in bovine brain tubulin lacking the type III isotype of b-tubulin. J Biol Chem 1990; 265: 1794-9.
8. Stubbs EB Jr, Fisher MA, Siegel GJ. Anti-tubulin antibodies in a sensorimotor neuropathy patient alter tubulin polymerization. Acta Neuropathol (Berl) 1998; 95: 302-5.
9. Norgren N, Rosengren L, Stigbrand T. Elevated neurofilament levels in neurological diseases. Brain Research 2003; 987: 25-31.
10. Semra YK, Seidi OA, Sharief MK. Heightened intrathecal release of axonal cytoskeletal proteins in multiple sclerosis is associated with progressive disease and clinical disability. J Neuroimmunol 2002; 122: 132-9.
11. Silber E, Semra YK, Gregson NA, Sharief MK. Patients with progressive multiple sclerosis have elevated antibodies to neurofilament subunit. Neurology 2002; 58: 1372-81.
12. Dighiero G, Guilbert B, Avrameas S. Naturally occurring antibodies against nine common antigens in humans sera. II. High incidence of monoclonal Ig exhibiting antibody activity against actin and tubulin and sharing antibody specificities with natural antibodies. J Immunol 1982; 128: 2788-92.
13. Avrameas S, Ternynck T. The natural autoantibodies system: between hypotheses and facts. Mol Immunol 1993; 30: 1133-42.
14. Terryberry JW, Thor G, Peter JB. Autoantibodies in neurodegenerative diseases: antigen specific frequencies and intrathecal analysis. Neurobiol Aging 1998; 19: 205-16.
15. Mathuranath PS, Nestor PJ, Berrios GE, Rakowicz W, Hodges JR. A brief cognitive test battery to differentiate Alzheimer's disease and frontotemporal dementia. Neurology 2000; 55: 1613-20.
16. Vyhnálek M, Škoda D, Varjassyová A, Hort J. Sémantická demence – důkaz mnohotvárnosti paměťových procesů. Neurol pro praxi 2005; 6: 330-332.
17. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. 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 1984; 34: 939-44.
18. Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 1993; 43: 250-60.
19. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998; 51: 1546-54.
20. Sjogren M, Blomberg M, Jonsson M, Wahlund LO, Edman A, Lind K et al. Neurofilament protein in cerebrospinal fluid: a marker of white matter changes. J Neurosci Res 2001; 66: 510-6.
21. Dráberová E, Lukas Z, Ivanyi D, Viklický V, Dráber P. Expression of class III ß-tubulin in normal and neoplastic human tissues. Histochem Cell Biol 1998; 109: 231-9.
22. Sjogren M, Wallin A. Pathophysiological aspects of frontotemporal dementia-emphasis on cytoskeleton proteins and autoimmunity. Mech Ageing Dev 2001; 122: 1923-35.
23. Wallin A, Sjögren M. Cerebrospinal fluid cytoskeleton proteins in patients with subcortical white-matter dementia. Mech Ageing Dev 2001; 122: 1937-49.
24. Rosengren LE, Karlsson JE, Sjogren M, Blennow K, Wallin A. Neurofilament protein levels in CSF are increased in dementia. Neurology 1999; 52: 1090–3.
25. Hu YY, He SS, Wang XC, Duan QH, Khatoon S, Iqbal K et al. Elevated levels of phosphorylated neurofilament proteins in cerebrospinal fluid of Alzheimer disease patients. Neurosci Lett 2002; 320: 156–60.
26. Prasannan L, Misek DE, Hinderer R, Michon J, Geiger JD, Hanash SM. Identification of beta-tubulin isoforms as tumor antigens in neuroblastoma. Clin Cancer Res 2000; 6: 3949-56.
27. Stubbs EB Jr, Fisher MA, Wilson JR, Siegel GJ. High-titer immunoglobulin M antibody to nerve-specific class III beta-tubulin in the serum of a patient with sensory demyelinating polyneuropathy. Muscle Nerve 1996; 19: 1638-9.
Štítky
Paediatric neurology Neurosurgery NeurologyČlánok vyšiel v časopise
Czech and Slovak Neurology and Neurosurgery
2007 Číslo 2
- Memantine Eases Daily Life for Patients and Caregivers
- Metamizole at a Glance and in Practice – Effective Non-Opioid Analgesic for All Ages
- Advances in the Treatment of Myasthenia Gravis on the Horizon
- Metamizole vs. Tramadol in Postoperative Analgesia
Najčítanejšie v tomto čísle
- Epilepsy and the Sleep-Waking Cycle
- The Current View of the Diagnostics and Therapy of Aphasias
- Complications of the Anterior Cervical Spine Surgery for a Degenerative Disease
- Worsening of Epileptic Seizures and Epilepsies due to Antiepileptic Drugs – is it Possible?