What are the relations between Lewy body disease and AD?
Several hospital based autopsy series indicate dementia with Lewy bodies (DLB) to be the second most common pathological subtype of degenerative dementia in elderly subjects. The majority of DLB cases have high densities of β amyloid senile plaques, whereas neocortical neurofibrillary tangle density is only slightly increased above age-matched normal control values and over tenfold lower than the average in Alzheimer’s disease. The interpretation of this Alzheimer type pathology is problematic, reflecting in part changing views about the neuropathological diagnosis of AD itself. AD is characterised by hyperphosphorylation of the microtubular associated protein tau, and DLB by neurofilament abnormalities including phosphorylation, ubiquitination, proteolysis, and cross-linking of constituent proteins. The two diseases appear therefore to be distinct at an ultrastructural and molecular level, a conclusion which is consistent with the fact that the clinical syndromes associated with DLB and AD are sufficiently differentiated to allow for accurate antemortem diagnosis.
KeywordsLewy Body Dementia With Lewy Body Alzheimer Pathology Lewy Body Disease Paired Helical Filament
Unable to display preview. Download preview PDF.
- Dickson DW, Ruan D, Crystal H, Mark MH, Davies P, Kress Y, Yen S-H (1991) Hippocampal degeneration differentiates diffuse Lewy body disease (DLBD) from Alzheimer’s disease: light and electron microscopic immunocytochemistry of CA2–3 neuntes specific to DLBD. Neurology 41: 1402–1409PubMedCrossRefGoogle Scholar
- 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 D, Burns A, Miller BL, Lovestone S, Collerton D, Jansen ENH, Ballard C, de Vos RAI, 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: 1113–1124PubMedCrossRefGoogle Scholar
- Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, Van Belle G, Berg L, and participating CERAD neuropathologists (1991) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) II. Standardisation of the neuropathological assessment of Alzheimer’s disease.Neurology 41: 479–486PubMedCrossRefGoogle Scholar
- Perry RH, Irving D, Blessed G, Perry EK, Fairbairn AF (1989) Clinically and neuropathologically distinct form of dementia in the elderly. Lancet: 166Google Scholar
- Perry RH, Jaros EB, Irving D, Scoones DJ, Brown A, McMeekin WM, Perry EK, Morris CM, Kelly PJ, Ince PG (1996) What is the neuropathological basis of dementia associated with Lewy bodies? In: Perry R, McKeith I, Perry E (eds) Dementia with Lewy bodies. Cambridge University Press, New York, pp 212–224CrossRefGoogle Scholar
- Saitoh T, Xia Y, Chen X, Masliah E, Galasko D, Shults C, Thal LJ, Hansen LA, Katzman R (1995) The CYP2D6B mutant allele is overrepresented in the Lewy body variant of Alzheimer’s disease. Am Neurol Assoc 110–112Google Scholar
- Trojanowski TJ, et al (National Institute on Aging and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer’s Disease (1998) Neurobiol Aging (in preparation)Google Scholar