Does striatal pathology distinguish Parkinson disease with dementia and dementia with Lewy bodies?
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The morphological differentiation of Parkinson disease with dementia (PDD) and dementia with Lewy bodies (DLB) is a matter of discussion. The objective of this study was to investigate the regional distribution of ß-amyloid (Aß) plaques, α-synuclein (AS), and pathology in both disorders. The basal ganglia from 17 age-matched patients of PDD and DLB each were immunohistochemically examined with variable degrees of associated Alzheimer pathology using antibodies to Aß, AS, and tau. DLB brains showed a significantly higher burden of (diffuse) amyloid plaques in the putamen and caudate nucleus and slightly more severe tau pathology than PDD brains despite similar neuritic Braak stages. Phases of Aß development in DLB brains often, but inconsistently, correlated with both neuritic Braak stages and severity of striatal Aß load, while these correlations were almost never seen in PDD cases with Alzheimer lesions. They also revealed a higher burden of AS-lesions (both Lewy neurites and Lewy bodies) than PDD cases that commonly had a paucity of all three types of lesion. The globus pallidus was virtually spared in both phenotypes. Differences in AS and Aß pathologies and much less of tau lesions in the striatum support a morphologic distinction between PDD and DLB, which may be of pathophysiologic importance, but the causes of these differences are unclear.
KeywordsParkinson disease with dementia Dementia with Lewy bodies Striatal α-synuclein Aß plaques
The study was supported by the Society for Support of Experimental Neurology, Vienna, Austria. The authors thank Mrs. V. Rappelsberger for excellent laboratory work, and Mr. E. Mitter-Ferstl, Ph.D., for secretarial and computer work.
- 5.Bibl M, Mollenhauer B, Esselmann H, Lewczuk P, Klafki HW, Sparbier K, Smirnov A, Cepek L, Trenkwalder C, Ruther E, Kornhuber J, Otto M, Wiltfang J (2006) CSF amyloid-beta-peptides in Alzheimer’s disease, dementia with Lewy bodies and Parkinson’s disease dementia. Brain 129:1177–1187PubMedCrossRefGoogle Scholar
- 17.Duyckaerts C (2002) Is Parkinson’s disease with dementia and dementia with Lewy body the same disease? Mov Disord 17(Suppl 5):S9Google Scholar
- 25.Hyman BT, Trojanowski JQ (1997) Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol 56:1095–1097PubMedCrossRefGoogle Scholar
- 37.Lees AJ (2002) Parkinson’s disease with dementia (PDD) is the same clinicopathological entity as dementia with Lewy bodies (DLB) (abstr). Mov Disord 17(Suppl 5):S9Google Scholar
- 38.Liang T, Noorigian JV, Duda JE (2006) Does striatal pathology distinguish DLB from PDD? Mov Disord 21(Suppl 13):S69–S70Google Scholar
- 40.McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, Salmon DP, Lowe J, Mirra SS, Byrne EJ, Lennox G, Quinn NP, Edwardson JA, Ince PG, Bergeron C, Burns A, Miller BL, Lovestone S, Collerton D, Jansen EN, Ballard C, de Vos RA, Wilcock GK, Jellinger KA, Perry RH (1996) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 47:1113–1124PubMedGoogle Scholar
- 43.McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN, Kaufer D, Kenny RA, Korczyn A, Kosaka K, Lee VM, Lees A, Litvan I, Londos E, Lopez OL, Minoshima S, Mizuno Y, Molina JA, Mukaetova-Ladinska EB, Pasquier F, Perry RH, Schulz JB, Trojanowski JQ, Yamada M (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65:1863–1872PubMedCrossRefGoogle Scholar
- 44.Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, van Belle G, Berg L (1991) The consortium to establish a registry for Alzheimer’s disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41:479–486PubMedGoogle Scholar
- 47.O’Brien J, Ames D, McKeith I, Chiu E (eds) (2006) Dementia with Lewy bodies and Parkinson’s disease dementia. Taylor & Francis, LondonGoogle Scholar
- 52.Porritt MJ, Kingsbury AE, Hughes AJ, Howells DW (2006) Striatal dopaminergic neurons are lost with Parkinson’s disease progression. Mov Disord (submitted)Google Scholar