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American Journal of Alzheimer's Disease and Other Dementias logoLink to American Journal of Alzheimer's Disease and Other Dementias
. 2008 Feb-Mar;23(1):97–102. doi: 10.1177/1533317507310565

Neuritic Pathology as a Correlate of Synaptic Loss in Dementia With Lewy Bodies

Gonzalo J Revuelta 1, Andrea Rosso 2, Carol F Lippa 3
PMCID: PMC10846257  PMID: 18276962

Abstract

Synaptic loss is present in Alzheimer's disease and correlates with the severity of dementia. Loss of synapses in dementia with Lewy bodies (DLB) does not correlate as clearly with cognitive status and its cause is unclear. To begin to understand the relationship between cognition and synaptic loss in DLB, we assessed immunoreactivity for the synaptic-terminal specific protein, synaptophysin, in the hippocampus in 14 DLB cases. Quantitative synaptic data were obtained using an Image-Pro semiautomated analysis system. We determined Braak stage, β-amyloid, Lewy bodies (LBs), and Lewy neurites (LN). We found significant correlations (r = 0.617, P < .01) between Braak stage and synaptophysin score and marginal correlation between LN score and synaptophysin loss ( r = 0.694, P < .06). Correlations of β-amyloid and of LB density with synaptophysin score were unimpressive. These data support the hypothesis that synaptic loss in DLB is related to neuritic degeneration.

Keywords: α-synuclein, β-amyloid, dementia with Lewy bodies, Braak stage, synapse, synaptic loss, tau

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Contributor Information

Gonzalo J. Revuelta, Department of Neurology, Drexel University College of Medicine, Philadelphia, Pennsylvania.

Andrea Rosso, Department of Neurology, Drexel University College of Medicine, Philadelphia, Pennsylvania.

Carol F. Lippa, Department of Neurology, Drexel University College of Medicine, Philadelphia, Pennsylvania, clippa@drexelmed.edu .

References

  1. McKeith IG, Galasko D., Kosaka K., et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology. 1996;47:1113-1124. [DOI] [PubMed] [Google Scholar]
  2. Marui W., Iseki E., Kato M., Akatsu H., Kosaka K. Pathological entity of dementia with Lewy bodies and its differentiation from Alzheimer's disease. Acta Neuropathol. 2004. ;108: 121-128. [DOI] [PubMed] [Google Scholar]
  3. Merdes AR, Hansen LA, Jeste DV, et al. Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies. Neurology. 2003. ;60: 1586-1590. [DOI] [PubMed] [Google Scholar]
  4. McKeith IG, Dickson DW, Lowe J., et al. Consortium on DLB. Diagnosis and management of dementia with Lewy bodies. Third report of the DLB consortium. Neurology . 2005;65:1864-1872. [DOI] [PubMed] [Google Scholar]
  5. Hamos JE, DeGennaro LJ, Drachman DA Synaptic loss in Alzheimer's disease and other dementias. Neurology. 1989;39:355-361. [DOI] [PubMed] [Google Scholar]
  6. Terry RD, Masliah E., Salmon DP, et al. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991;30:572-580. [DOI] [PubMed] [Google Scholar]
  7. Hansen LA, Daniel SE, Wilcock GK, Love S. Frontal cortical synapthophysin in Lewy body diseases: relation to Alzheimer's disease and dementia. J Neurol Neurosurg Psychiatry. 1998;64:653-656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brown DF, Risser RC, Bigio EH, et al. Neocortical synapse density and Braak stage in the Lewy body variant of Alzheimer disease: a comparison with classic Alzheimer disease and normal aging. J Neuropathol Exp Neurol. 1998;57:955-960. [DOI] [PubMed] [Google Scholar]
  9. Hamos JE, DeGennaro LJ, Drachman DA Synaptic loss in Alzheimer's disease and other dementias. Neurology. 1989;39:355-361. [DOI] [PubMed] [Google Scholar]
  10. Lippa CF, Hamos JE, Pulaski-Salo D., DeGennaro LJ, Drachman DA Alzheimer's disease and aging: effects on perforant pathway perikarya and synapses. Neurobiol Aging. 1992;13:405-411. [DOI] [PubMed] [Google Scholar]
  11. Braak H., Alafuzoff I., Arzberger T., Kretzschmar H., Del Tredici K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol (Berl) . 2006; 112:389-404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Brown DF, Dababo MA, Bigio EH, et al. Neuropathologic evidence that the Lewy body variant of Alzheimer disease represents coexistence of Alzheimer disease and idiopathic Parkinson disease. J Neuropathol Exp Neurol. 1998; 57:39-46. [DOI] [PubMed] [Google Scholar]
  13. Popescu A., Lippa CF, Lee VM, Trojanowski JQ Lewy bodies in the amygdala: increase of alpha-synuclein aggregates in neurodegenerative diseases with tau-based inclusions. Arch Neurol. 2004;61:1915-1919. [DOI] [PubMed] [Google Scholar]
  14. Lippa CF, Pulaski-Salo D., Dickson DW, Smith TW Alzheimer's disease, Lewy body disease and aging: a comparative study of the perforant pathway. J Neurol Sci. 1997;147:161-166. [DOI] [PubMed] [Google Scholar]
  15. Samuel W., Alford M., Hofstetter R., Hansen L. Dementia with Lewy bodies versus pure Alzheimer disease: differences in cognition, neuropathology, cholinergic dysfunction, and synapse density. J Neuropathol Exp Neurol. 1997;56:499-508. [DOI] [PubMed] [Google Scholar]
  16. Kowalska A. The beta-amyloid cascade hypothesis: a sequence of events leading to neurodegeneration in Alzheimer's disease. Neurol Neurochir Pol. 2004;38: 405-411. [PubMed] [Google Scholar]
  17. Klucken J., McLean PJ, Gomez-Tortosa E., Ingelsson M., Hyman BT Neuritic alteration and neural system dysfunction in Alzheimer's disease and dementia with Lewy bodies. Neurochem Res. 2003;28:1683-1691. [DOI] [PubMed] [Google Scholar]
  18. Hashimoto M. , Masliah E. Cycles of aberrant synaptic sprouting and neurodegeneration in Alzheimer's and dementia with Lewy bodies. Neurochem Res. 2003; 28:1743-1756. [DOI] [PubMed] [Google Scholar]
  19. Masliah E., Mallory M., DeTeresa R., Alford M., Hansen L. Differing patterns of aberrant neuronal sprouting in Alzheimer's disease with and without Lewy bodies. Brain Res. 1993;617:258-266. [DOI] [PubMed] [Google Scholar]
  20. Coleman P., Federoff H., Kurlan R. A focus on the synapse for neuroprotection in Alzheimer disease and other dementias. Neurology. 2004;63:1155-1162. [DOI] [PubMed] [Google Scholar]
  21. Deramecourt V., Bombois S., Maurage CA, et al. Biochemical staging of synucleinopathy and amyloid deposition in dementia with Lewy bodies. J Neuropathol Exp Neurol. 2006;65:278-288. [DOI] [PubMed] [Google Scholar]

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