Lewy Bodies in Alzheimer Disease-One or Two Diseases?

Bergeron, C.; Pollanen, Michael S.

doi:10.1097/00002093-198900000-00002

Cited by 56 publications

(16 citation statements)

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“…A detailed neuropathological examination was performed on all AD cases as previously described (Bergeron and Pollanen, 1989). The criteria for the diagnosis of AD included the presence of both neuritic plaques (NPs) and neurofibrillary tangles (NFTs) in both neocortex and hippocampus in the absence of any other degenerative process.…”

Section: Methodsmentioning

confidence: 99%

Brain α‐Ketoglutarate Dehydrotenase Complex Activity in Alzheimer's Disease

Mastrogiacomo

Bergeron

Kish

1993

Journal of Neurochemistry

172

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We measured the activity of the alpha-ketoglutarate dehydrogenase complex (alpha-KGDHC), a rate-limiting Krebs cycle enzyme, in postmortem brain samples from 38 controls and 30 neuropathologically confirmed Alzheimer's disease (AD) cases, in both the presence and absence of thiamine pyrophosphate (TPP), the enzyme's cofactor. Statistically significant correlations between brain pH and lactate levels and alpha-KGDHC activity in the controls were observed, suggesting an influence of agonal status on the activity of alpha-KGDHC. As compared with the controls, mean alpha-KGDHC activity, with added TPP, was significantly (p < 0.005) reduced in AD brain in frontal (-56%), temporal (-60%), and parietal (-68%) cortices, with the reductions (-25 to -53%) in the occipital cortex, hippocampus, amygdala, and caudate failing to reach statistical significance. In the absence of exogenously administered TPP, mean alpha-KGDHC activity was reduced to a slightly greater extent in all seven AD brain areas (-39 to -83%), with the reductions now reaching statistical significance in the four cerebral cortical areas and hippocampus. A statistically significant negative correlation was observed between alpha-KGDHC activity and neurofibrillary tangle count in AD parietal cortex, the brain area exhibiting the most marked reduction in enzyme activity; this suggests that the enzyme activity reduction in AD brain may be related to the disease process and severity. In each brain area examined, TPP produced a greater stimulatory effect on alpha-KGDHC activity in the AD group (23-280% mean stimulation) as compared with the controls (-4 to +50%); this TPP effect could be explained by reduced endogenous TPP levels in AD brain.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Methodsmentioning

confidence: 99%

Brain α‐Ketoglutarate Dehydrotenase Complex Activity in Alzheimer's Disease

Mastrogiacomo

Bergeron

Kish

1993

Journal of Neurochemistry

172

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“…Tangles were quantified as previously described (Bergeron and Pollanen, 1989), revealing tangle densities of 0.24 and 0.09/mmz (in middle temporal gyrus, Bielschowsky silver staining), which was judged to be insignificant to contaminate the LB fractions ( Fig. 1).…”

Section: Source Of Tissuementioning

confidence: 99%

Detergent‐Insoluble Cortical Lewy Body Fibrils Share Epitopes with Neurofilament and τ

Pollanen

Bergeron

Weyer

1992

Journal of Neurochemistry

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Lewy bodies are cytoskeletal inclusions associated with neuronal injury and death in idiopathic Parkinson's disease and other neurodegenerative disorders. The chemical composition of the 8-10-nm fibrils of the Lewy body is unknown, although they are related to both normal cytoskeletal elements and paired helical filaments of Alzheimer neurofibrillary tangles. From the Lewy body-rich cerebral cortex of patients with diffuse Lewy body disease we have isolated intact Lewy bodies using a high salt buffer/nonionic detergent gradient centrifugation procedure and extracted the constitutive fibrils with urea and sodium dodecyl sulfate. Urea/detergent-resistant Lewy body fibrils were solubilized with formic acid and found to contain a single protein band of 68 kDa, which was not found in identically prepared normal brain homogenates. The Lewy body derived-polypeptide was recognized on immunoblots by a polyclonal antibody that reacted with both the 68-kDa neurofilament subunit and the microtubule-associated protein tau. The 68-kDa Lewy body protein was not labeled by the monoclonal antibody tau-1 despite prior in vitro enzymatic dephosphorylation. We conclude that the detergent-insoluble component of the cortical Lewy body fibril shares epitopes with neurofilament and tau and may be a posttranslationally modified derivative of either neurofilament or tau with substantially altered biochemical and immunologic properties.

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“…Recent attention has focused on a possible contribu tion for cortical Lewy bodies (CLB) in the pathogenesis of dementia in Alzheimer's disease (AD) because CLB are common in the brains of patients clinically diagnosed as either probable or possible AD [1][2][3]. One current study suggested that Lewy body disease (LBD) is a subtype of AD [4], Other researchers maintain that AD patients with numerous CLB may actually have two independent disor ders (AD and LBD) [5].…”

Section: Introductionmentioning

confidence: 99%

Familial Alzheimer’s Disease and Cortical Lewy Bodies: Is There a Genetic Susceptibility Factor?

Lippa

Smith

Nee

et al. 1995

Dement Geriatr Cogn Disord

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The reason for the occurrence of Lewy body disease (LBD) in Alzheimer''s disease (AD) patients in unknown. If brains from etiologically different AD groups differ in their tendency to develop cortical Lewy bodies, the concurrence of LBD in AD patients may be a manifestation of the AD process in specific AD subsets. To address this issue, we counted cortical Lewy bodies in AD patients with genetic abnormalities on chromosome 14 (n = 19), and chromosome 21 (n = 3), sporadic AD (n = 27), Down''s Syndrome (n = 1) and control (n = 26) patients. Cortical Lewy bodies were occasionally present in AD patients with long-duration disease in most of the above AD subgroups, but were not present in any of our age-matched control cases. We suggest that cortical Lewy body formation may be an intrinsic part of the late pathologic changes of AD regardless of etiology and that it is not specific to any of the AD subtypes studied.

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Lewy Bodies in Alzheimer Disease-One or Two Diseases?

Cited by 56 publications

References 0 publications

Brain α‐Ketoglutarate Dehydrotenase Complex Activity in Alzheimer's Disease

Brain α‐Ketoglutarate Dehydrotenase Complex Activity in Alzheimer's Disease

Detergent‐Insoluble Cortical Lewy Body Fibrils Share Epitopes with Neurofilament and τ

Familial Alzheimer’s Disease and Cortical Lewy Bodies: Is There a Genetic Susceptibility Factor?

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