Dementia Associated With Lewy Bodies

Abstract

IN THIS issue, Sabbagh et al¹ attempt to shed light on the pathophysiology of the Lewy body variant of Alzheimer disease (LBV). This is another important step in a long journey. The association of Lewy bodies with Parkinson disease was made in 1912; the first report of Lewy bodies in association with dementia, in 1961.² Since then, owing to the development of immunostaining techniques for the Lewy body–associated protein ubiquitin, and more recently for I-synuclein, an increasingly strong link has been established between the presence of extranigral Lewy bodies and the development of dementing illness in which extrapyramidal symptoms may follow the onset of dementia or may not occur at all. In fact, late-life dementia associated with Lewy bodies is probably second in prevalence only to Alzheimer disease (AD), occurring in approximately 20% of persons diagnosed while alive with probable AD.³ Is this the coincidence of 2 diseases (after all, AD is highly prevalent) with 2 fundamentally different pathogenetic processes that lead to dementia-associated neuronal inclusion bodies? One process might be abnormal phosphorylation of the microtubule-associated protein τ producing neurofibrillary tangles. The other process might involve abnormal I-synuclein metabolism resulting in the formation of Lewy bodies. The latter possibility has been recently heightened by the discovery of a mutation in the I-synuclein gene of a family with familial Parkinson disease.⁴