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,
ß-amyloid intraneuronal accumulation and a rare formation of ß-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 Lacanà, Alberto Diaspro,
Maria Adelaide Pronzato, Antonella Vitali, Roberta Roncarati, Paola
Strocchi, Damiano Zaccheo, Luciano D’Adamio, Massimo Tabaton
Neuronal apoptosis is accompanied by amyloid ß-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 ß-protein (Aß) 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 Aß occurred, in spite of a 20% reduction
of cellular metabolism and an unchanged AßPP expression. The
increased intracellular Aß reactivity largely colocalized with a
marker of ER. Inhibition of caspases blocked the cleavage at the
C-terminus of AßPP, but only partially rescued Aß overproduction
caused by staurosporine treatment. Our findings suggest that PCD
fosters the physiological pathways of Aß 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 AßPP
processing during PCD.
Commentary on the Borghi et al.
manuscript:
Pages 39-40
Sanjay W. Pimplikar
AßPP, 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
RETURN
TO INDEX
top |