Journal of Alzheimer's Disease - Volume 4, issue 1

Authors: Zatta, Paolo | Zambenedetti, Pamela | Stella, Maria Pia | Licastro, Federico

Article Type: Research Article

Abstract: Cholesterol is considered a risk factor in vascular dementia as well as in Alzheimer's disease. Several biochemical, epidemiological and genetic aspects established a correlation between cholesterol concentration and Alzheimer's disease. Microglia activation, astrocytosis with metallothionein-I-II overexpression, amyloid β intraneuronal accumulation and a rare formation of amyloid β extracellular positive deposits were the major immunohistochemical features observed in the brain of high cholesterol-fed animals. The relevance on the cholesterol metabolism in Alzheimer's disease pathogenesis is also discussed.

Keywords: Aβ metabolism, Astrocyte activation, microgliosis, Cholesterol-fed rabbit, Metallothionein

DOI: 10.3233/JAD-2002-4101

Citation: Journal of Alzheimer's Disease, vol. 4, no. 1, pp. 1-9, 2002

Authors: SantaCruz, K.S. | Tasaki, C.S. | Kim, R.C. | Cotman, C.W.

Article Type: Research Article

Abstract: In order to study the clinical overlap between neuropathologically defined Lewy body disease (LBD) and Alzheimer's disease, we examined the brains of 37 demented and 13 non-demented subjects. Nigral Lewy bodies (LBs) were present in 16/37 dementia patients, 13 of which had LBD. Eight of these 13 were clinically indistinguishable from AD patients, and in these cases isocortical neurofibrillary tangle (NFT) formation was rare. Thus, although the two conditions were clinically similar in this series, LBD could be distinguished from AD pathologically not only by the presence of nigral LBs but also by the relative paucity of isocortical NFTs.

DOI: 10.3233/JAD-2002-4102

Citation: Journal of Alzheimer's Disease, vol. 4, no. 1, pp. 11-17, 2002

Authors: Bassett, Casey N. | Swift, Larry L. | Montine, Kathleen S. | Markesbery, William R. | Montine, Thomas J.

Article Type: Research Article

Abstract: Recent studies of cerebrospinal fluid (CSF) have shown increased oxidation of CSF lipoproteins in Alzheimer's disease (AD) patients, and neurotoxicity from oxidized CSF lipoproteins in culture. Since inheritance of different alleles of the apolipoprotein (apo) E gene is a risk factor for AD and apoE is the major lipoprotein trafficking molecule in brain, we hypothesized that apoE may modify the pathogenesis of AD by directing the delivery of oxidized CSF lipoproteins to neurons. To test this hypothesis, we adapted a method previously used with isolated plasma lipoproteins to specifically label lipid particles in situ in native CSF and quantified …their delivery to human SK-N-BE(2)C neuroblastoma cells. CSF lipoproteins were delivered to neuronal cells largely through apoE-dependent processes. Importantly, CSF lipoproteins from AD patients were delivered more efficiently than CSF lipoproteins from age-matched controls; this effect was not associated with apoE genotype or degree of CSF lipoprotein oxidation but was associated with apoE monomer concentration that tended to be lower in AD patients. The inverse relationship between apoE monomer concentration and CSF lipoprotein delivery was duplicated in SK-N-BE(2)C cells, but not human astrocytoma cells, using artificial lipid particles and purified human apoE. These results suggest that lipoproteins in CSF from AD patients are delivered more efficiently to neurons than are CSF lipoproteins from controls, and that this abnormality may be explained largely by variations in CSF apoE concentration. Show more

Keywords: Alzheimer's disease, cerebrospinal fluid, DiI, lipoproteins, oxidation

DOI: 10.3233/JAD-2002-4103

Citation: Journal of Alzheimer's Disease, vol. 4, no. 1, pp. 19-30, 2002

Authors: Borghi, Roberta | Pellegrini, Luca | Lacaná, Emanuela | Diaspro, Alberto | Pronzato, Maria Adelaide | Vitali, Antonella | Roncarati, Roberta | Strocchi, Paola | Zaccheo, Damiano | D'Adamio, Luciano | Tabaton, Massimo

Article Type: Research Article

Abstract: A series of evidences suggests that enhanced susceptibility to programmed cell death (PCD) is a major pathogenetic factor in Alzheimer's disease (AD). We investigated this issue, analyzing amyloid β-protein (Aβ) production in a model of neuronal PCD, induced by staurosporine in a murine neuroblastoma cell line. When PCD was induced, a 280–290% secreted Aβ occurred, in spite of a 20% metabolism and an unchanged AβPP expression. The increased intracellular Aβ reactivity largely colocalized with a marker of ER. Inhibition of caspases blocked the cleavage at the C-terminus ofβPP, but only partially rescued Aβ overproduction caused by staurosporine treatment. Our findings …suggest that PCD fosters the physiological pathways of Aβ production characteristic of neuronal cells, and they confirm the theory that unbalance of PCD is a central event in AD pathogenesis. Moreover, our data indicate that still unidentified cellular mechanisms, other than caspases activation, are responsible of the specific alteration of AβPP processing during PCD. Show more

DOI: 10.3233/JAD-2002-4104

Citation: Journal of Alzheimer's Disease, vol. 4, no. 1, pp. 31-37, 2002

Authors: Pimplikar, Sanjay W.

Article Type: Research Article

DOI: 10.3233/JAD-2002-4105

Citation: Journal of Alzheimer's Disease, vol. 4, no. 1, pp. 39-40, 2002

Article Type: Book Review

DOI: 10.3233/JAD-2002-4106

Citation: Journal of Alzheimer's Disease, vol. 4, no. 1, pp. 41-42, 2002

Article Type: Book Review

DOI: 10.3233/JAD-2002-4107

Citation: Journal of Alzheimer's Disease, vol. 4, no. 1, pp. 43-44, 2002

Article Type: Abstract

DOI: 10.3233/JAD-2002-4108

Citation: Journal of Alzheimer's Disease, vol. 4, no. 1, pp. 45-69, 2002