Alzheimer's disease: biological aspects, therapeutic perspectives and diagnostic tools

被引:54
作者
Di Carlo, M. [1 ]
Giacomazza, D. [2 ]
San Biagio, P. L. [2 ]
机构
[1] CNR, IBIM, I-90146 Palermo, Italy
[2] CNR, Ist Biofis IBF, I-90146 Palermo, Italy
关键词
CEREBRAL GLUCOSE-METABOLISM; LONGITUDINAL PET EVALUATION; AMYLOID PRECURSOR PROTEIN; FACTOR GENE-THERAPY; NEURAL STEM-CELLS; A-BETA OLIGOMERS; CEREBROSPINAL-FLUID; APOLIPOPROTEIN-E; TAU-PROTEIN; OXIDATIVE STRESS;
D O I
10.1088/0953-8984/24/24/244102
中图分类号
O469 [凝聚态物理学];
学科分类号
070205 ;
摘要
Alzheimer's disease (AD) is the most common form of dementia among older people. Dementia is an irreversible brain disorder that seriously affects a person's ability to carry out daily activities. It is characterized by loss of cognitive functioning and behavioral abilities, to such an extent that it interferes with the daily life and activities of the affected patients. Although it is still unknown how the disease process begins, it seems that brain damage starts a decade or more before problems become evident. Scientific data seem to indicate that changes in the generation or the degradation of the amyloid-b peptide (A beta) lead to the formation of aggregated structures that are the triggering molecular events in the pathogenic cascade of AD. This review summarizes some characteristic features of A beta misfolding and aggregation and how cell damage and death mechanisms are induced by these supramolecular and toxic structures. Further, some interventions for the early diagnosis of AD are described and in the last part the potential therapeutic strategies adoptable to slow down, or better block, the progression of the pathology are reported.
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页数:17
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共 171 条
[1]   Longitudinal PET evaluation of cerebral metabolic decline in dementia: A potential outcome measure in Alzheimer's disease treatment studies [J].
Alexander, GE ;
Chen, K ;
Pietrini, P ;
Rapoport, SI ;
Reiman, EM .
AMERICAN JOURNAL OF PSYCHIATRY, 2002, 159 (05) :738-745
[2]   Mitochondria and vascular lesions as a central target for the development of Alzheimer's disease and Alzheimer disease-like pathology in transgenic mice [J].
Aliev, G ;
Seyidova, D ;
Lamb, BT ;
Obrenovich, ME ;
Siedlak, SL ;
Vinters, HV ;
Friedland, RP ;
LaManna, JC ;
Smith, MA ;
Perry, G .
NEUROLOGICAL RESEARCH, 2003, 25 (06) :665-674
[3]   Aspects of β-amyloid as a biomarker for Alzheimer's disease [J].
Andreasson, Ulf ;
Portelius, Erik ;
Andersson, Malin E. ;
Blennow, Kaj ;
Zetterberg, Henrik .
BIOMARKERS IN MEDICINE, 2007, 1 (01) :59-78
[4]   Multiple quantum solid-state NMR indicates a parallel, not antiparallel, organization of β-sheets in Alzheimer's β-amyloid fibrils [J].
Antzutkin, ON ;
Balbach, JJ ;
Leapman, RD ;
Rizzo, NW ;
Reed, J ;
Tycko, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (24) :13045-13050
[5]   Supramolecular structural constraints on Alzheimer's β-amyloid fibrils from electron microscopy and solid-state nuclear magnetic resonance [J].
Antzutkin, ON ;
Leapman, RD ;
Balbach, JJ ;
Tycko, R .
BIOCHEMISTRY, 2002, 41 (51) :15436-15450
[6]   Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum [J].
Axe, Elizabeth L. ;
Walker, Simon A. ;
Manifava, Maria ;
Chandra, Priya ;
Roderick, H. Llewelyn ;
Habermann, Anja ;
Griffiths, Gareth ;
Ktistakis, Nicholas T. .
JOURNAL OF CELL BIOLOGY, 2008, 182 (04) :685-701
[7]   Inflammatory mediator and β-amyloid (25-35)-induced ceramide generation and iNOS expression are inhibited by vitamin E [J].
Ayasolla, K ;
Khan, M ;
Singh, AK ;
Singh, I .
FREE RADICAL BIOLOGY AND MEDICINE, 2004, 37 (03) :325-338
[8]   The cortical signature of prodromal AD Regional thinning predicts mild AD dementia [J].
Bakkour, Akram ;
Morris, John C. ;
Dickerson, Bradford C. .
NEUROLOGY, 2009, 72 (12) :1048-1055
[9]   Supramolecular structure in full-length Alzheimer's β-amyloid fibrils:: Evidence for a parallel β-sheet organization from solid-state nuclear magnetic resonance [J].
Balbach, JJ ;
Petkova, AT ;
Oyler, NA ;
Antzutkin, ON ;
Gordon, DJ ;
Meredith, SC ;
Tycko, R .
BIOPHYSICAL JOURNAL, 2002, 83 (02) :1205-1216
[10]   Direct observation of Aβ amyloid fibril growth and inhibition [J].
Ban, T ;
Hoshino, M ;
Takahashi, S ;
Hamada, D ;
Hasegawa, K ;
Naiki, H ;
Goto, Y .
JOURNAL OF MOLECULAR BIOLOGY, 2004, 344 (03) :757-767