Role of β-Amyloid in the Diagnosis of Neurodegenerative Diseases: Diffuse Lewy Body Disease Versus Alzheimer’s Disease

  • Amy L. Ullrich
  • Christine M. Noga
  • Debra J. Magnuson
  • John M. Lee
Part of the Advances in Behavioral Biology book series (ABBI, volume 44)


Deposition of β-amyloid senile plaques in the neuropil and the formation of intracellular neurofibrillary tangles are the histopathological hallmarks of both sporadic and familial forms of Alzheimer’s disease (AD). Excess β-amyloid, formed from abnormal processing of β-amyloid precursor protein (β-APP) coded for on chromosome 21, can also be found in aged individuals with Down’s syndrome (Trisomy 21) as well as in the recently described cases of diffuse Lewy body disease (DLBD) (Gibb et al., 1989; Kosaka, 1993; Kuzuhara and Yoshimura, 1993). Patients with the pure form of DLBD are characterized clinically by progressive dementia with fluctuating confusional states and visual hallucinations, followed later by Parkinsonian symptoms (Byrne et al., 1989; Forstl et al., 1993; Kosaka, et al., 1980; and Perry et al., 1993). Parkinsonism rarely is the presenting symptom. Neuropathological findings include Lewy bodies both in the neuromelanin containing cells of the substantia nigra as well as in the neocortex but few, if any, neurofibrillary tangles. The occurrence of DLBD as well as the Lewy body variant of AD (LBVAD) is not as rare as previously thought (Gibb et al., 1989; Forstl et al., 1993). The LBVAD has features of both DLBD and AD. It has been found that, when combined, both types of Lewy body disease are the second leading cause of non-vascular dementia following classical AD.


Lewy Body Neurofibrillary Tangle Brodmann Area Neuritic Plaque Lewy Body Dementia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bancher, C., Lassmann, H., Budka, H., Jellinger, K., Grundke-Iqbal, I., Iqbal, K., Wiche, G., Seitelberger, F., and Wisniewski, H.M., 1989, An antigenic profile of Lewy bodies:Immunocytochemical indication for protein phosphorylation and ubiquitination, J. Neuropathol. Exp. Neurol. 48: 81–92.PubMedCrossRefGoogle Scholar
  2. Byrne, E.J., Lennox, G., and Lowe, J., 1989, Diffuse Lewy body disease: Clinical features in 15 cases, J. Neurol. Neurosurg. Psychiatry 52: 709–717.PubMedCrossRefGoogle Scholar
  3. Dickson, D.W., Crystal, H., Mattiace, L.A., Kress, Y., Schwager!, A., Ksiezak-Reding, H., Davies, P., and Yen S.-H. C., 1989, Diffuse Lewy body disease: Light and electron microscopic immunocytochemistry of senile plaques, Acta Neuropathol. 78: 572–584.PubMedCrossRefGoogle Scholar
  4. Drewes, G., Lichtenberg-Kraag, B., Dozing, F., Mandelkow, E.-M., Biemat, J., Goris, J., Doree, M., and Mandelkow, E., 1992, Mitogen activated protein (MAP) kinase transforms tau protein into an Alzheimer-like state, EMBO J. 11:2131–2138.Google Scholar
  5. Forstl, H., Burns, A., Luthert, P., Cairns, N., and Levy, R., 1993, The Lewy-body variant of Alzheimer’s disease: Clinical and pathological findings, Br.J. Psychiatry 162: 385–392.PubMedCrossRefGoogle Scholar
  6. Galloway, P.G., Grundke-Iqbal, I., Iqbal, K., and Perry, G., 1988, Lewy bodies contain epitopes both shared and distinct from Alzheimer neurofibrillary tangles, J. Neuropathol. Exp. Neurol. 47: 654–663.PubMedCrossRefGoogle Scholar
  7. Galloway, P.G., Bergeron, C., and Perry, G., 1989, The presence of tau distinguishes Lewy bodies of diffuse Lewy body disease from those of idiopathic Parkinson disease, Neurosci. Lett. 100: 6–10.PubMedCrossRefGoogle Scholar
  8. Gibb, W.R.G., Mountjoy, C.Q., Mann, D.M.A., and Lees, A.J., 1989, A pathological study of the association between Lewy body disease and Alzheimer’s disease, J. Neurol. Neurosurg. Psychiatry 52: 701–708.Google Scholar
  9. Kosaka, K., Matsushita, M., Oyanagi, S., and Mehraein, P., 1980, A clinicopathological study of the “Lewy body disease”, Psychiatr. Neurol. Jpn. 82: 292–311.Google Scholar
  10. Kosaka, K.,1993, Dementia and neuropathology in Lewy body disease, Adv. Neurol. 60:456–463. Kuzuhara, S., and Yoshimura, M., 1993, Clinical and neuropathological aspects of diffuse Lewy body diseasein in the elderly, Adv. Neurol. 60: 464–469.Google Scholar
  11. Lantos, P.L., Luthert, P.J., Hanger, D., Anderton, B.H., Mullan M., and Rossor, M., 1992, Familial Alzheimer’s disease with the amyloid precursor protein 717 mutation and sporadic Alzheimer’s disease have the same cytoskeletal pathology, Neurosci. Lett. 137 (2): 221–224.PubMedCrossRefGoogle Scholar
  12. Lennox, G., Lowe, J., Landon, M., Byrne, E.J., Mayer, R.J., and Godwin-Austen, R.B., 1989, Diffuse Lewy body disease: Correlative neuropathology using anti-ubiquitin immunocytochemistry, J. Neurol. Neurosurg. Psychiatry 52: 1236–1247.PubMedCrossRefGoogle Scholar
  13. Lichtenberg-Kraag, B., Mandelkow, E.-M., Biemat, J., Steiner, B., Schroter, C., Gustke, N., Meyer, H.E., and Mandelkow, E., 1992, Phosphorylation-dependent epitopes of neurofilament antibodies on tau protein and relationship with Alzheimer tau, Proc. Natl. Acad. Sci. USA 89: 5384–5388.PubMedCrossRefGoogle Scholar
  14. Mattson, M.P., Tomaselli, K.J., and Russell E.R., 1993, Calcium-destabilizing and neurodegenerative effects of aggregated ß-amyloid peptide are attenuated by basic FGF, Brain Res. 621: 35–49.PubMedCrossRefGoogle Scholar
  15. Mullan, M., and Crawford, F., 1993, Genetic and molecular advances in Alzheimer’s disease, Trends Neurosci. 16: 398–403.PubMedCrossRefGoogle Scholar
  16. Perry, E.K., Irving, D., Kerwin, J.M., McKeith, I.G., Thompson, P., Collerton, D., Fairbairn, A.F., Ince, P.G., Morris, C.M., Cheng, A.V., and Perry, R.H., 1993, Cholinergie transmitter and neurotrophic activities in Lewy body dementia: Similarity to Parkinson’s and distinction from Alzheimer’s disease, Alzheimer Dis. Assoc. Disord. 7: 69–79.Google Scholar
  17. Pollanen, M.S., Bergeron, C., and Weyer, L., 1992, Detergent-insoluble cortical Lewy body fibrils share epitopes with neurofilament and tau, J. Neurochem. 58: 1953–1956.PubMedCrossRefGoogle Scholar
  18. Pollanen, M.S., Dickson, D.W., and Bergeron, C., 1993, Pathology and biology of the Lewy body, J. Neuropathol. Exp. Neurol. 52: 183–191.PubMedCrossRefGoogle Scholar
  19. Raghavan, R., Khin-Nu, C., Brown, A., Irving, D., Ince, P.G., Day, K., Tyrer, S.P., Perry, R.H., 1993, Detection of Lewy bodies in Trisomy 21 (Down’s Syndrome), Can. J. Neurol. Sci. 20: 48–51.PubMedGoogle Scholar
  20. Schmidt, M.L., Murray, J., Lee, M-Y., Hill, W.D., Wertkin, A., and Trojanowski, J.Q., 1991, Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies, Am. J. Pathol. 139: 53–65.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Amy L. Ullrich
    • 1
  • Christine M. Noga
    • 1
  • Debra J. Magnuson
    • 2
  • John M. Lee
    • 2
  1. 1.Stritch School of MedicineLoyola University ChicagoMaywoodUSA
  2. 2.Department of Pathology Section of NeuropathologyLoyola University Chicago Stritch School of MedicineMaywoodUSA

Personalised recommendations