Pathological entity of dementia with Lewy bodies and its differentiation from Alzheimer?s disease

Abstract

We reclassified the pathological subtypes of dementia with Lewy bodies (DLB), based on both Lewy pathology and Alzheimer pathology, to clarify the pathological entity of DLB and the boundary between DLB and Alzheimer's disease (AD) in autopsied cases, using both pathological and immunohistochemical methods. DLB was classified as either limbic type or neocortical type according to the degree of Lewy pathology including Lewy bodies (LB) and LB-related neurites by our staging, and was classified as pure form, common form or AD form according to the degree of Alzheimer pathology including neurofibrillary tangles (NFT) and amyloid deposits by Braak staging. These combined subtypes were lined up on a spectrum, not only with Lewy pathology but also with other DLB-related pathologies including Alzheimer pathology, neuronal loss in the substantia nigra, spongiform change in the transentorhinal cortex and LB-related neurites in the CA2-3 region. In contrast, the Lewy pathology of AD did not meet the stages of Lewy pathology in DLB, and there were scarcely any similarities in other DLB-related pathologies between AD and DLB. In addition, the Lewy pathology of AD had characteristics different from that of DLB, including the coexistence rate of LB with NFT, and the immunohistochemical and immunoelectron microscopic findings of LB and LB-related neurites. These findings suggest that DLB is a distinctive pathological entity that can be differentiated from AD, although it shows some pathological subtypes.

Serum Heart-Type Fatty Acid-Binding Protein and Cerebrospinal Fluid Tau: Marker Candidates for Dementia with Lewy Bodies

“…Today a definite diagnosis of the underlying neurodegenerative syndrome still requires neuropathological confirmation [2][3][4] . Early and accurate diagnosis becomes more and more important, since novel and disease-specific intervention trials are being planned, since unnecessary medication and tests are to be avoided, and since the costs for dementia care soar [5] .…”

Comprehensive Genetic and Mutation Analysis of Familial Dementia with Lewy Bodies Linked to 2q35-q36

“…The identification of the underlying complex genetic defect will reveal the first novel causal gene for DLB. Of interest, Lewy body pathology has also been reported to be present in a substantial number of AD brains and, vice versa, AD pathology has been detected to various extent in autopsied DLB brains [38], suggesting either overlapping or interacting pathogenic mechanisms. Therefore, we are convinced that the study of the mutation spectrum of this novel gene in DLB and other neurodegenerative brain diseases with overlapping clinical and/or pathological features, such as AD, will not only provide a better understanding of the molecular pathogenic cascades of these diseases but might also highlight important mechanistic links between them.…”

Dementia with Lewy Bodies: Current Concepts

“…Braak et al [104] have proposed a new staging system for PD with six stages of the disease beginning with presymptomatic LBs in the medulla and olfactory bulb with progressive stages ascending to the neocortex. Although it is intended for PD staging, stages IV-VI overlap with the system proposed by Marui et al [102,103] and these higher stages may be valid for the staging of DLB [105] .…”

“…Recently, new methods for staging have been proposed. A four-stage classifi cation of DLB follows progression of the disease from the amygdala to the limbic cortex followed by the neocortex [102,103] . Braak et al [104] have proposed a new staging system for PD with six stages of the disease beginning with presymptomatic LBs in the medulla and olfactory bulb with progressive stages ascending to the neocortex.…”