Catecholamine-based treatment in ad patients: Expectations and delusions

Frontiers in Aging Neuroscience

Volumn 7, Issue MAY, 2015, Pages

  Stefani, Alessandro ^a,b   Olivola, Enrica ^a   Liguori, Claudio ^c   Hainsworth, Atticus H ^d   Saviozzi, Valentina ^a   Angileri, Giacoma ^a   D'Angelo, Vincenza ^a   Galati, Salvatore ^e   Pierantozzi, Mariangela ^a  

^a UNIVERSITY OF ROME TOR VERGATA   (Italy)

^b IRCCS FONDAZIONE SANTA LUCIA   (Italy)

^c TOR VERGATA UNIVERSITY HOSPITAL   (Italy)

^d ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

^e REGIONAL HOSPITAL OF LUGANO   (Switzerland)

Author keywords

Alzheimer's disease; Catecholamine; CSF; Dopamine; Monoaminooxidase inhibitors

Indexed keywords

5 HYDROXYINDOLEACETIC ACID; APOMORPHINE; CATECHOLAMINE; DOPAMINE; FLUORODEOXYGLUCOSE; HOMOVANILLIC ACID; LEVODOPA; NORADRENALIN; OXIDOPAMINE; PRAZOSIN; RASAGILINE; ROTIGOTINE; SELEGILINE; SEROTONIN; TYROSINE 3 MONOOXYGENASE;

ALZHEIMER DISEASE; ARTICLE; CEREBROSPINAL FLUID; COHORT ANALYSIS; DISEASE COURSE; DISEASE DURATION; FRONTOTEMPORAL DEMENTIA; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HIPPOCAMPUS; HUMAN; LUMBAR PUNCTURE; MORRIS WATER MAZE TEST; MULTICENTER STUDY (TOPIC); NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; POSITRON EMISSION TOMOGRAPHY; PREFRONTAL CORTEX; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK FACTOR; TREND STUDY;

EID: 84931262149     PISSN: None     EISSN: 16634365     Source Type: Journal    
DOI: 10.3389/fnagi.2015.00067     Document Type: Article

References (79)

1. Agnoli, A., Fabbrini, G., Fioravanti, M., and Martucci, N. (1992). CBF and cognitive evaluation of Alzheimer type patients before and after IMAO-B treatment: A pilot study. Eur. Neuropsychopharmacol. 2, 31-35. doi: 10.1016/0924-977X(92)90033-5
2. Bekar, L. K., Wei, H. S., and Nedergaard, M. (2012). The locus coeruleus-norepinephrine network optimizes coupling of cerebral blood volume with oxygen demand. J. Cereb. Blood Flow Metab. 32, 2135-2145. doi:10.1038/jcbfm.2012.115
3. Bhavna, Md, S., Ali, M., Ali, R., Bhatnagar, A., Baboota, S., et al. (2014). Donepezil nanosuspension intended for nose to brain targeting: in vitro and in vivo safety evaluation. Int. J. Biol. Macromol. 67, 418-425. doi:10.1016/j.ijbiomac.2014.03.022
4. Birks, J., and Flicker, L. (2003). Selegiline for Alzheimer's disease. Cochrane Database Syst. Rev. 1:CD000442. doi:10.1002/14651858.CD000442
5. Bolea, I., Gella, A., and Unzeta, M. (2013). Propargylamine-derived multitarget-directed ligands: fighting Alzheimer's disease with monoamine oxidase inhibitors. J. Neural Transm. 120, 893-902. doi:10.1007/s00702-012-0948-y
6. Borroni, B., Costanzi, C., and Padovani, A. (2010). Genetic susceptibility to behavioral and psychological symptoms in Alzheimer disease. Curr. Alzheimer Res. 7, 158-164. doi:10.2174/156720510790691173
7. Brusa, L., Bassi, A., Stefani, A., Pierantozzi, M., Peppe, A., Caramia, M. D., et al. (2003). Pramipexole in comparison to l-dopa: a neuropsychological study. J. Neural Transm. 110, 373-380. doi:10.1007/s00702-002-0811-7
8. 123I-FP-CIT study in the early stages of the disease. Eur. J. Nucl. Med. Mol. Imaging 41, 2137-2143. doi:10.1007/s00259-014-2841-4
9. Dar, T. A., Sheikh, I. A., Ganie, S. A., Ali, R., Singh, L. R., Gan, S. H., et al. (2014). Molecular linkages between diabetes and Alzheimer's disease: current scenario and future prospects. CNS Neurol. Disord. Drug Targets 13, 290-298. doi:10.2174/18715273113126660135
10. De Souza, L. C., Sarazin, M., Teixeira-Júnior, A. L., Caramelli, P., Santos, A. E., and Dubois, B. (2014). Biological markers of Alzheimer's disease. Arq. Neuropsiquiatr. 72, 227-231. doi:10.1590/0004-282X20130233
11. Diomedi, M., and Stefani, A. (2014). Hemodynamic changes in Alzheimer's disease: a leading role behind the curtain? Commentary on "CSF Aβ1-42 combined with neuroimaging biomarkers in the early detection, diagnosis and prediction of Alzheimer's disease" by Lista et al. Alzheimers Dement. doi:10.1016/j.jalz.2014.10.004
12. Dysken, M. W., Sano, M., and Asthana, S. (2014). Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA 311, 33-44. doi:10.1001/jama.2013.282834
13. Emre, M., Poewe, W., De Deyn, P. P., Barone, P., Kulisevsky, J., Pourcher, E., et al. (2014). Long-term safety of rivastigmine in Parkinson disease dementia: an open-label, randomized study. Clin. Neuropharmacol. 37, 9-16. doi:10.1097/WNF.0000000000000010
14. Esposito, Z., Belli, L., Toniolo, S., Sancesario, G., Bianconi, C., and Martorana, A. (2013). Amyloid β, glutamate, excitotoxicity in Alzheimer's disease: are we on the right track? The more the disease progresses, the more the uneffectiveness of antidementia drugs emerges. CNS Neurosci. Ther. 19, 549-555. doi:10.1111/cns.12095
15. Fitzgerald, P. J. (2010). Is elevated norepinephrine an etiological factor in some cases of Alzheimer's disease? Curr. Alzheimer Res. 7, 506-516. doi:10.2174/156720510792231775
16. Frakey, L. L., Salloway, S., Buelow, M., and Malloy, P. J. (2012). A randomized, double-blind, placebo-controlled trial of modafinil for the treatment of apathy in individuals with mild-to-moderate Alzheimer's disease. J. Clin. Psychiatry 73, 796-801. doi:10.4088/JCP.10m06708
17. Freedman, M., Rewilak, D., Xerri, T., Cohen, S., Gordon, A. S., Shandling, M., et al. (1998). L-deprenyl in Alzheimer's disease: cognitive and behavioral effects. Neurology 50, 660-668. doi:10.1212/WNL.50.3.660
18. Geda, Y. E., Schneider, L. S., Gitlin, L. N., Miller, D. S., Smith, G. S., Bell, J., et al. (2013). Neuropsychiatric symptoms in Alzheimer's disease: past progress and anticipation of the future. Alzheimers Dement. 9, 602-608. doi:10.1016/j.jalz.2012.12.001
19. Geerts, H., Roberts, P., Spiros, A., and Carr, R. (2013). A strategy for developing new treatment paradigms for neuropsychiatric and neurocognitive symptoms in Alzheimer's disease. Front. Pharmacol. 4:47. doi:10.3389/fphar.2013.00047
20. Gibbs, M. E., Maksel, D., Gibbs, Z., Hou, X., Summers, R. J., and Small, D. H. (2010). Memory loss caused by beta-amyloid protein is rescued by a beta(3)-adrenoceptor agonist. Neurobiol. Aging 31, 614-624. doi:10.1016/j.neurobiolaging.2008.05.018
21. Gliebus, G., and Lippa, C. F. (2007). The influence of beta-blockers on delayed memory function in people with cognitive impairment. Am. J. Alzheimers Dis. Other Demen. 22, 57-61. doi:10.1177/1533317506295889
22. Goldstein, D. S., Sullivan, P., Holmes, C., Miller, G. W., Alter, S., Strong, R., et al. (2013). Determinants of buildup of the toxic dopamine metabolite DOPAL in Parkinson's disease. J. Neurochem. 126, 591-603. doi:10.1111/jnc.12345
23. Hampel, H., Lista, S., Teipel, S. J., Garaci, F., Nisticò, R., Blennow, K., et al. (2014). Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: a long-range point of view beyond 2020. Biochem. Pharmacol. 88, 426-449. doi:10.1016/j.bcp.2013.11.009
24. Hanagasi, H. A., Gurvit, H., Unsalan, P., Horozoglu, H., Tuncer, N., Feyzioglu, A., et al. (2011). The effects of rasagiline on cognitive deficits in Parkinson's disease patients without dementia: a randomized, double-blind, placebo-controlled, multicenter study. Mov. Disord. 26, 1851-1858. doi:10.1002/mds.23738
25. Hardenacke, K., Kuhn, J., Lenartz, D., Maarouf, M., Mai, J. K., Bartsch, C., et al. (2013). Stimulate or degenerate: deep brain stimulation of the nucleus basalis Meynert in Alzheimer dementia. World Neurosurg. 80, e35-e43. doi:10.1016/j.wneu.2012.12.005
26. Herrmann, N., Rothenburg, L. S., Black, S. E., Ryan, M., Liu, B. A., Busto, U. E., et al. (2008). Methylphenidate for the treatment of apathy in Alzheimer disease: prediction of response using dextroamphetamine challenge. J. Clin. Psychopharmacol. 28, 296-301. doi:10.1097/JCP.0b013e318172b479
27. Himeno, E., Ohyagi, Y., Ma, L., Nakamura, N., Miyoshi, K., Sakae, N., et al. (2011). Apomorphine treatment in Alzheimer mice promoting amyloid-b degradation. Ann. Neurol. 69, 248-256. doi:10.1002/ana.22319
28. Ismail, Z., Nguyen, M. Q., Fischer, C. E., Schweizer, T. A., Mulsant, B. H., and Mamo, D. (2011). Neurobiology of delusions in Alzheimer's disease. Curr. Psychiatry Rep. 13, 211-218. doi:10.1007/s11920-011-0195-1
29. Itoh, A., Nitta, A., Nadai, M., Nishimura, K., Hirose, M., Hasegawa, T., et al. (1996). Dysfunction of cholinergic and dopaminergic neuronal systems in beta-amyloid protein-infused rats. J. Neurochem. 66, 1113-1117. doi:10.1046/j.1471-4159.1996.66031113.x
30. Kadowaki Horita, T., Kobayashi, M., Mori, A., Jenner, P., and Kanda, T. (2013). Effects of the adenosine A2A antagonist istradefylline on cognitive performance in rats with a 6-OHDA lesion in prefrontal cortex. Psychopharmacology (Berl.) 230, 345-352. doi:10.1007/s00213-013-3158-x
31. Kalinin, S., Polak, P. E., Lin, S. X., Sakharkar, A. J., Pandey, S. C., and Feinstein, D. L. (2012). The noradrenaline precursor L-DOPS reduces pathology in a mouse model of Alzheimer's disease. Neurobiol. Aging 33, 1651-1663. doi:10.1016/j.neurobiolaging.2011.04.012
32. Katsouri, L., Vizcaychipi, M. P., McArthur, S., Harrison, I., Suárez-Calvet, M., Lleo, A., et al. (2013). Prazosin, an α(1)-adrenoceptor antagonist, prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer's disease. Neurobiol. Aging 34, 1105-1115. doi:10.1016/j.neurobiolaging.2012.09.010
33. Kemppainen, N., Laine, M., Laakso, M. P., Kaasinen, V., Någren, K., Vahlberg, T., et al. (2003). Hippocampal dopamine D2 receptors correlate with memory functions in Alzheimer's disease. Eur. J. Neurosci. 18, 149-154. doi:10.1046/j.1460-9568.2003.02716.x
34. -1 cell neurotoxicity independently of monoamine oxidase inhibition. Exp. Neurol. 166, 458-464. doi:10.1006/exnr.2000.7517
35. Koch, G., Di Lorenzo, F., Bonnì, S., Ponzo, V., Caltagirone, C., and Martorana, A. (2012). Impaired LTP- but not LTD-like cortical plasticity in Alzheimer's disease patients. J. Alzheimers Dis. 31, 593-599. doi:10.3233/JAD-2012-120532
36. Kumar, U., and Patel, S. C. (2007). Immunohistochemical localization of dopamine receptor subtypes (D1ReD5R) in Alzheimer's disease brain. Brain Res. 1131, 187-196. doi:10.1016/j.brainres.2006.10.049
37. Kupershmidt, L., Amit, T., Bar-Am, O., Weinreb, O., and Youdim, M. B. (2012). Multi-target, neuroprotective and neurorestorative M30 improves cognitive impairment and reduces Alzheimer's-like neuropathology and age-related alterations in mice. Mol. Neurobiol. 46, 217-220. doi:10.1007/s12035-012-8304-7
38. Langbaum, J. B., Fleisher, A. S., Chen, K., Ayutyanont, N., Lopera, F., Quiroz, Y. T., et al. (2013). Ushering in the study and treatment of preclinical Alzheimer disease. Nat. Rev. Neurol. 9, 371-381. doi:10.1038/nrneurol.2013.107
39. Laxton, A. W., and Lozano, A. M. (2013). Deep brain stimulation for the treatment of Alzheimer disease and dementias. World Neurosurg. 80, e1-e8. doi:10.1016/j.wneu.2012.06.028
40. Liguori, C., Stefani, A., Sancesario, G., Sancesario, G. M., Marciani, M. G., and Pierantozzi, M. (2014). CSF lactate levels, τ proteins, cognitive decline: a dynamic relationship in Alzheimer's disease. J. Neurol. Neurosurg. Psychiatr. doi:10.1136/jnnp-2014-308577
41. 1-42 combined with neuroimaging biomarkers in the early detection, diagnosis and prediction of Alzheimer's disease. Alzheimers Dement. 10, 381-392. doi:10.1016/j.jalz.2013.04.506
42. Lu, C., Zhou, Q., Yan, J., Du, Z., Huang, L., and Li, X. (2013). A novel series of tacrine-selegiline hybrids with cholinesterase and monoamine oxidase inhibition activities for the treatment of Alzheimer's disease. Eur. J. Med. Chem. 62, 745-753. doi:10.1016/j.ejmech.2013.01.039
43. Mancuso, C., Siciliano, R., Barone, E., Butterfield, D. A., and Preziosi, P. (2011). Pharmacologists and Alzheimer disease therapy: to boldly go where no scientist has gone before. Expert Opin. Investig. Drugs 20, 1243-1261. doi:10.1517/13543784.2011.601740
44. Martorana, A., Stefani, A., Palmieri, M. G., Esposito, Z., Bernardi, G., Sancesario, G., et al. (2008). L-dopa modulates motor cortex excitability in Alzheimer's disease patients. J. Neural Transm. 115, 1313-1319. doi:10.1007/s00702-008-0082-z
45. Martorana, A., Mori, F., Esposito, Z., Kusayanagi, H., Monteleone, F., Codecà, C., et al. (2009). Dopamine modulates cholinergic cortical excitability in Alzheimer's disease patients. Neuropsychopharmacology 34, 2323-2328. doi:10.1038/npp.2009.60
46. Martorana, A., Esposito, Z., and Koch, G. (2010). Beyond the cholinergic hypothesis: do current drugs work in Alzheimer's disease? CNS Neurosci. Ther. 16, 235-245. doi:10.1111/j.1755-5949.2010.00175.x
47. Martorana, A., Semprini, R., and Koch, G. (2011). "Clinical profile of Alzheimer's disease non-responder patient," in Advanced Understanding of Neuro- degenerative Diseases, ed. C. Raymond Chuen-Chung (Rijeka: InTech), 156-168. [ISBN 978-953-307-529-7].
48. Martorana, A., Di Lorenzo, F., Esposito, Z., Lo Giudice, T., Bernardi, G., Caltagirone, C., et al. (2013). Dopamine D2-agonist rotigotine effects on cortical excitability and central cholinergic transmission in Alzheimer's disease patients. Neuropharmacology 64, 108-113. doi:10.1016/j.neuropharm.2012.07.015
49. McKeith, I., O'Brien, J., Walker, Z., Tatsch, K., Booij, J., Darcourt, J., et al. (2007). Sensitivity and specificity of dopamine transporter imaging with 123I.FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicenter study. Lancet Neurol. 6, 305-313. doi:10.1016/S1474-4422(07)70057-1
50. Mizukami, K., Hatanaka, K., Tanaka, Y., Sato, S., and Asada, T. (2009). Therapeutic effects of the selective serotonin noradrenaline reuptake inhibitor milnacipran on depressive symptoms in patients with Alzheimer's disease. Prog. Neuropsychopharmacol. Biol. Psychiatry 33, 349-352. doi:10.1016/j.pnpbp.2008.12.019
51. Mura, E., Lanni, C., Preda, S., Pistoia, F., Sarà, M., Racchi, M., et al. (2010). Beta-amyloid: a disease target or a synaptic regulator affecting age-related neurotransmitter changes? Curr. Pharm. Des. 16, 672-683. doi:10.2174/138161210790883723
52. Mustapic, M., Presecki, P., Pivac, N., Mimica, N., Hof, P. R., Simic, G., et al. (2013). Genotype-independent decrease in plasma dopamine beta-hydroxylase activity in Alzheimer's disease. Prog. Neuropsychopharmacol. Biol. Psychiatry 1, 94-99. doi:10.1016/j.pnpbp.2013.02.002
53. Padala, P. R., Burke, W. J., Shostrom, V. K., Bhatia, S. C., Wengel, S. P., Potter, J. F., et al. (2010). Methylphenidate for apathy and functional status in dementia of the Alzheimer type. Am. J. Geriatr. Psychiatry 18, 371-374. doi:10.1097/JGP.0b013e3181cabcf6
54. Perani, D., Schillaci, O., Padovani, A., Nobili, F. M., Iaccarino, L., Della Rosa, P. A., et al. (2014). A survey of FDG- and amyloid-PET imaging in dementia and GRADE analysis. Biomed Res. Int. 2014, 785039. doi:10.1155/2014/785039
55. Raskind, M. A., Peskind, E. R., Holmes, C., and Goldstein, D. S. (1999). Patterns of cerebrospinal fluid catechols support increased central noradrenergic responsiveness in aging and Alzheimer's disease. Biol. Psychiatry 46, 756-765. doi:10.1016/S0006-3223(99)00008-6
56. Robertson, I. H. (2013). A noradrenergic theory of cognitive reserve: implications for Alzheimer's disease. Neurobiol. Aging 34, 298-308. doi:10.1016/j.neurobiolaging.2012.05.019
57. Sano, M., Ernesto, C., Thomas, R. G., Klauber, M. R., Schafer, K., Grundman, M., et al. (1997). A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's disease cooperative study. N. Engl. J. Med. 336, 1216-1222. doi:10.1056/NEJM199704243361704
58. Schneider, L. S., Mangialasche, F., Andreasen, N., Feldman, H., Giacobini, E., Jones, R., et al. (2014). Clinical trials and late-stage drug development for Alzheimer's disease: an appraisal from 1984 to 2014. Intern. Med. 275, 251-283. doi:10.1111/joim.12191
59. Schneider, L. S., Olin, J. T., and Pawluczyk, S. (1993). A double-blind crossover pilot study of l-deprenyl (selegiline) combined with cholinesterase inhibitor in Alzheimer's disease. Am. J. Psychiatry 150, 321-323. doi:10.1176/ajp.150.2.321
60. Scott, T. J., O'Connor, A. C., Link, A. N., and Beaulieu, T. J. (2014). Economic analysis of opportunities to accelerate Alzheimer's disease research and development. Ann. N. Y. Acad. Sci. 1313, 17-34. doi:10.1111/nyas.12417
61. Sepehry, A. A., Lee, P. E., Hsiung, G. Y., Beattie, B. L., and Jacova, C. (2012). Effect of selective serotonin reuptake inhibitors in Alzheimer's disease with comorbid depression: a meta-analysis of depression and cognitive outcomes. Drugs Aging 29, 793-806. doi:10.1007/s40266-012-0012-5
62. Stefani, A., Bernardini, S., Panella, M., Pierantozzi, M., Nuccetelli, M., Koch, G., et al. (2005). AD with subcortical white matter lesions and vascular dementia: CSF markers for differential diagnosis. J. Neurol. Sci. 237, 83-88. doi:10.1016/j.jns.2005.05.016
63. Stefani, A., Martorana, A., Bernardini, S., Panella, M., Mercati, F., Orlacchio, A., et al. (2006). CSF markers in Alzheimer disease patients are not related to the different degree of cognitive impairment. J. Neurol. Sci. 251, 124-128. doi:10.1016/j.jns.2006.09.014
64. Stefani, A., Sancesario, G., Pierantozzi, M., Leone, G., Galati, S., Hainsworth, A. H., et al. (2009). CSF biomarkers, impairment of cerebral hemodynamics and degree of cognitive decline in Alzheimer's and mixed dementia. J. Neurol. Sci. 283, 109-115. doi:10.1016/j.jns.2009.02.343
65. Stefani, A., Brusa, L., Olivola, E., Pierantozzi, M., and Martorana, A. (2012). CSF and clinical hallmarks of subcortical dementias: focus on DLB and PDD. J. Neural Transm. 119, 861-875. doi:10.1007/s00702-012-0820-0
66. Szot, P., White, S. S., Greenup, J. L., Leverenza, J. B., Peskind, E. R., and Raskind, M. A. (2006). Compensatory changes in the noradrenergic nervous system in the locus coeruleus and hippocampus of postmortem subjects with Alzheimer's disease and dementia with Lewy bodies. J. Neurosci. 26, 467-478. doi:10.1523/JNEUROSCI.4265-05.2006
67. Tariot, P. N., Goldstein, B., Podgorski, C. A., Cox, C., and Frambes, N. (1998). Short-term administration of selegiline for mild-to-moderate dementia of the Alzheimer's type. Am. J. Geriatr. Psychiatry 6, 145-154. doi:10.1097/00019442-199821000-00008
68. Tatsch, K., and Poepper, I. (2013). Nigrostriatal dopamine terminal imaging with dopamine transporter SPCET: an update. J. Nucl. Med. 54, 1331-1338. doi:10.2967/jnumed.112.105379
69. Thiratmatrakul, S., Yenjai, C., Waiwut, P., Vajragupta, O., Reubroycharoen, P., Tohda, M., et al. (2014). Synthesis, biological evaluation and molecular modeling study of novel tacrine-carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer's disease. Eur. J. Med. Chem. 75, 21-30. doi:10.1016/j.ejmech.2014.01.020
70. Thomas, T. (2000). Monoamine oxidase-B inhibitors in the treatment of Alzheimer's disease. Neurobiol. Aging 21, 343-348. doi:10.1016/S0197-4580(00)00100-7
71. Tolbert, S. R., and Fuller, M. A. (1996). Selegiline in treatment of behavioral and cognitive symptoms of Alzheimer disease. Ann. Pharmacother. 30, 1122-1129.
72. Vilalta-Franch, J., Calvó-Perxas, L., Garre-Olmo, J., Turró-Garriga, O., and López-Pousa, S. J. (2013). Apathy syndrome in Alzheimer's disease epidemiology: prevalence, incidence, persistence, and risk and mortality factors. J. Alzheimers Dis. 33, 535-543. doi:10.3233/JAD-2012-120913
73. Wang, L. Y., Shofer, J. B., Rohde, K., Hart, K. L., Hoff, D. J., McFall, Y. H., et al. (2009). Prazosin for the treatment of behavioral symptoms in patients with Alzheimer disease with agitation and aggression. Am. J. Geriatr. Psychiatry 17, 744-751. doi:10.1097/JGP.0b013e3181ab8c61
74. Wirz, K. T., Keitel, S., Swaab, D. F., Verhaagen, J., and Bossers, K. (2014). Early molecular changes in Alzheimer disease: can we catch the disease in its presymptomatic phase? J. Alzheimers Dis. 38, 719-740. doi:10.3233/JAD-130920
75. Yan, R., and Vassar, R. (2014). Targeting the β secretase BACE1 for Alzheimer's disease therapy. Lancet Neurol. 13, 319-329. doi:10.1016/S1474-4422(13)70276-X
76. Yu, J. T., Wang, N. D., Ma, T., Jiang, H., Guan, J., and Tan, L. (2011). Roles of β-adrenergic receptors in Alzheimer's disease: implications for novel therapeutics. Brain Res. Bull. 84, 111-117. doi:10.1016/j.brainresbull.2010.11.004
77. Zarow, C., Lyness, S. A., Mortimer, J. A., and Chui, H. C. (2003). Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch. Neurol. 60, 337-341. doi:10.1001/archneur.60.3.337
78. Zheng, H., Amit, T., Bar-Am, O., Fridkin, M., Youdim, M. B., and Mandel, S. A. (2012). From anti-Parkinson's drug rasagiline to novel multitarget iron chelators with acetylcholinesterase and monoamine oxidase inhibitory and neuroprotective properties for Alzheimer's disease. J. Alzheimers Dis. 30, 1-16. doi:10.3233/JAD-2012-120013
79. Zweig, R. M., Ross, C. A., Hedreen, J. C., Steele, C., Cardillo, J. E., Whitehouse, P. J., et al. (1989). Neuropathology of aminergic nuclei in Alzheimer's disease. Prog. Clin. Biol. Res. 317, 353-365.