Clinical and neuropathological correlates of dementia with Lewy bodies.
Dementia with Lewy bodies (DLB) is characterized pathologically by widespread Lewy body (LB) neuronal inclusions in the brain, but the contribution of LBs to the clinical syndrome of dementia and parkinsonism is unclear. In a clinical-pathological study of 25 cases with DLB, we examined the regional neuroanatomical distribution of Lewy-related pathology using alpha-synuclein immunostaining to evaluate the relationship between LBs, neuronal loss, Alzheimer-type changes, and the clinical phenotype. Compared to traditional ubiquitin immunostaining, alpha-synuclein immunohistochemistry was more specific and slightly more sensitive, staining about 5% more intracytoplasmic structures. There was a consistent pattern of vulnerability to LB formation across subcortical, paralimbic, limbic, and neocortical structures, which was independent of concomitant Alzheimer-type changes. There were no significant differences in regional LB densities among patients with or without cognitive fluctuations, visual hallucinations, delusions, recurrent falls or parkinsonism. Duration of disease correlated weakly with LB density. There was no neuronal loss in superior temporal sulcus or entorhinal cortex in pure DLB cases compared to nondemented controls. Thus, DLB is characterized by a specific neuroanatomical vulnerability to LB pathology, distinct from AD pathology, with a complicated relationship to clinical symptoms.
Gómez-Tortosa
E
E
Alzheimer Disease Research Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Irizarry
M C
MC
Gómez-Isla
T
T
Hyman
B T
BT
D000368:Aged; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology*; D020961:Lewy Body Disease / Q000473:pathology* / Q000503:physiopathology* / Q000523:psychology; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009474:Neurons / Q000473:pathology; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein