A.Toledano & al.
536
51. Cohen, A. D.; Rabinovici, G. D.; Mathis, C. A.; Jagust, W. J.; Klunk, W. E.; Ikonomovic, M. D.
Using Pittsburgh Compound B for in vivo PET imaging of fibrillar amyloid-‐beta. Adv
Pharmacol
64
, 27-‐81 (2012).
52. Armstrong, R. A. The interface between Alzheimer's disease, normal aging, and related
disorders. Curr Aging Sci
1
, 122-‐132 (2008).
53. Saunders, A. M.; Strittmatter, W. J.; Schmechel, D.; George-‐Hyslop, P. H.; Pericak-‐Vance, M.
A.; Joo, S. H.; Rosi, B. L.; Gusella, J. F.; Crapper-‐MacLachlan, D. R.; Alberts, M. J. Association
of apolipoprotein E allele epsilon 4 with late-‐onset familial and sporadic Alzheimer's
disease. Neurology
43
, 1467-‐1472 (1993).
54. Ringman, J. M.; Coppola, G. New genes and new insights from old genes: update on
Alzheimer disease. Continuum (Minneap Minn)
19
, 358-‐71 (2013).
55. Serrano-‐Pozo, A.; Qian, J.; Monsell, S. E.; Frosch, M. P.; Betensky, R.A.; Hyman, B. T.
Examination of the clinicopathologic continuum of Alzheimer disease in the autopsy
cohort of the National Alzheimer Coordinating Center. J Neuropathol Exp Neurol. 72,1182-‐
1192 (2013).
56. Pappolla, M. A. La Neuropatología y la Biología Molecular de la Enfermedad de Alzheimer.
En:.
Neuropathología. Diagnóstico y Clínica
. Cruz-‐Sánchez F.F., Ed.; Edimsa, Barcelona,
2000; p 543.
57. Penke, B.; Tóth, A. M.; Földi, I.; Szűcs, M.; Janáky, T. Intraneuronal β-‐amyloid and its
interactions with proteins and subcellular organelles. Electrophoresis
33,
3608-‐3616
(2012).
58. Delacourte, A. General and dramatic glial reaction in Alzheimer brains. Neurology
40
, 33-‐
37 (1990)
59. Dickson; C., Vickers, J. C. The morphological phenotype of b-‐amyloid plaques and
associated neuritic changes in Alzheimer's. Neuroscience
105
, 99-‐107 (2001).
60. Wegiel, J.; Wang, K. C.; Tarnawski, M.; Lach, B. Microglia cells are the driving force in
fibrillar plaque formation, whereas astrocytes are a leading factor in plague degradation.
Acta Neuropathol
100
, 356–364 (2000).
61. Bartus, R. T.; Dean, R. L.; 3rd, Beer, B. Lippa AS The cholinergic hypothesis of geriatric
memory dysfunction. Science
30,
217(4558):408-‐14 (1982).
62. Mann, D. M.; Yates, P. O.; Marcyniuk, B. Alzheimer's presenile dementia, senile dementia of
Alzheimer type and Down's syndrome in middle age form an age related continuum of
pathological changes. Neuropathol Appl Neurobiol
10
, 185-‐207 (1984).
63. Mecocci, P. Oxidative stress in mild cognitive impairment and Alzheimer disease: a
continuum. J Alzheimers Dis. 2004 Apr;6(2):159-‐63.
64. Nixon, R. A.; Yang, D. S.; Lee, J. H. Neurodegenerative lysosomal disorders: a continuum
from development to late age. Autophagy
4
, 590-‐9 (2008).
65. Toledano, A.; Álvarez, MI.; Rivas, L.; Lacruz, C.; Martínez-‐Rodríguez, R. Amyloid precursor
protein in the cerebellar cortex of Alzheimer 's disease patients devoid of cerebellar ß-‐
amyloid deposits. Immunocytochemical study of five cases. J Neural Trans
106
, 1151-‐
1169 (1999).
66. Toledano, A.
Hypotheses concerning the aetiology of the Alzheimer's disease.
Pharmacopsychiat
21
, 17-‐25 (1988).
67. Toledano, A.; Bentura, M. Pyritinol facilitates the recovery of cortical cholinergic deficits
caused by nucleus basalis lesions J Neural Transm [P-‐D Section]
7
, 195-‐209 (1994).
68. Drachman, D. A.; Leavitt, J. Human memory and the cholinergic system: relationship to
aging? Arch Neurol
30
, 113–121 (1974).
69. Coyle, J. T.; Price, D. L.; De Long, M. R. Alzheimer's disease: a disorder of cortical cholinergic
innervation. Science
219
, 1184-‐1190 (1983).
70. Schneider, L. S. Alzheimer disease pharmacologic treatment and treatment research.
Continuum (Minneap Minn).
19
, 339-‐357 (2013).
71. Van Hoesen, G. W.; Augustinack, J. C.; Dierking, J.; Redman, S. J.; Thangavel, R. The
parahippocampal gyrus in Alzheimer's disease. Clinical and preclinical neuroanatomical
correlates. Ann N Y Acad Sci
911
, 254-‐274 (2000).
72. de Toledo-‐Morrell, L.; Goncharova, I.; Dickerson, B.; Wilson, R. S.; Bennett, D. A. From
healthy aging to early Alzheimer's disease: in vivo detection of entorhinal cortex atrophy.
Ann N Y Acad Sci
911
, 240-‐53 (2000).
73. Stricker, N. H.;(1), Chang, Y. L.; Fennema-‐Notestine, C.; Delano-‐Wood, L.; Salmon, D. P.;
Bondi, M. W.; Dale, A. M. Alzheimer's Disease Neuroimaging Initiative. Distinct profiles of
