Volume 4, Number 1, February 2002

Pages 1-9
Paolo Zatta, Pamela Zambenedetti, Maria Pia Stella and Federico Licastro
Astrocytosis, microgliosis, metallothionein-I-II and amyloid expression in high cholesterol-fed rabbits
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 intraneuronal accumulation and a rare formation of -amyloid 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.

Pages 11-17
SantaCruz KS, Tasaki CS, Kim RC, Cotman CW
Brainstem and cortical Lewy bodies in patients presenting clinically with Alzheimer’s disease
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.

Pages 19-30
Casey N. Bassett, Larry L. Swift, Kathleen S. Montine, William R. Markesbery, and Thomas J. Montine
Cerebrospinal fluid lipoprotein delivery to human neuronal cells is increased in Alzheimer’s disease and is dependent on ApoE monomer concentration
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.

Pages 31-37
Roberta Borghi, Luca Pellegrini, Emanuela Lacan, Alberto Diaspro, Maria Adelaide Pronzato, Antonella Vitali, Roberta Roncarati, Paola Strocchi, Damiano Zaccheo, Luciano D’Adamio, Massimo Tabaton
Neuronal apoptosis is accompanied by amyloid -protein accumulation in the endoplasmic reticulum
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 -protein (A) production in a model of neuronal PCD, induced by staurosporine in a murine neuroblastoma cell line. When PCD was induced, a 280-290% increase of respectively intracellular and secreted A occurred, in spite of a 20% reduction of cellular metabolism and an unchanged APP expression. The increased intracellular A reactivity largely colocalized with a marker of ER. Inhibition of caspases blocked the cleavage at the C-terminus of APP, but only partially rescued A overproduction caused by staurosporine treatment. Our findings suggest that PCD fosters the physiological pathways of A 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 APP processing during PCD.

Commentary on the Borghi et al. manuscript:

    Pages 39-40
    Sanjay W. Pimplikar
    APP, Apoptosis and Alzheimer’s disease

Pages 41-42
Book Review: Research and Practice in Alzheimer's Disease, Volume 5. B.Vellas, B.Winblad, M.N.Grundman, L.J.Fitten, H.Feldman, and E.Giacobini (Eds), Serdi Publishers, Paris & Springer Publishing Company, New York, 2001, 265 pp.  Reviewed by Kurt Jellinger

Pages 43-44
Book Review: Parkinson’s Disease: Methods and Protocols. M.M. Mouradian (Ed), Humana Press Inc., Totawa, New Jersey, 2001, 336pp.  Reviewed by Rudy Castellani

Pages 45-68
Proceedings from the First International Conference on Alzheimer’s Disease and Related Neurodegenerative Disorders in Wuhan, China