Skip to main content
Erschienen in: NeuroMolecular Medicine 1/2013

01.03.2013 | Original Paper

Decreased Levels of Circulating Adiponectin in Mild Cognitive Impairment and Alzheimer’s Disease

verfasst von: Antonio L. Teixeira, Breno S. Diniz, Alline C. Campos, Aline S. Miranda, Natalia P. Rocha, Leda L. Talib, Wagner F. Gattaz, Orestes V. Forlenza

Erschienen in: NeuroMolecular Medicine | Ausgabe 1/2013

Einloggen, um Zugang zu erhalten

Abstract

Adiponectin, an adipocytokine released by the adipose tissue and has important roles in the metabolic regulation and inflammatory control, may play an important roles in the physiopathology of psychiatric and neurodegenerative disorders. The aim of the present work was to evaluate adiponectin serum levels in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) as compared to cognitively healthy elders and to correlate these levels with clinical and cognitive parameters. We further evaluated whether circulating adiponectin levels could predict progression from MCI to Alzheimer’s disease upon follow-up. We recruited 157 subjects (41 with AD, 65 with MCI and 51 elderly controls) in the baseline assessment. Follow-up data were available for 54 subjects with MCI and 43 controls in whom we ascertained the conversion to AD and the progression of cognitive impairment. Adiponectin was assayed by sandwich ELISA. Serum levels of adiponectin were significantly lower in MCI and AD as compared to controls (p < 0.001). After controlling for age, educational level and APOE genotype, adiponectin levels remained significantly reduced in these groups (p < 0.001). Circulating adiponectin levels did not predict cognitive decline in the elderly controls (i.e., progression from normal cognition to MCI) or progression to Alzheimer’s disease in subjects with MCI. We conclude that lower levels of adiponectin were associated with cognitive dysfunction, though it did not predict additional cognitive decline and conversion to dementia in this cohort of elderly subjects. Decreased adiponectin may be a surrogate marker of the pathological process in AD, linking clinical comorbidities, inflammation and cognitive dysfunction.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
Zurück zum Zitat Calvani, M., Scarfone, A., Granato, L., Mora, E. V., Nanni, G., Castagneto, M., et al. (2004). Restoration of adiponectin pulsatility in severely obese subjects after weight loss. Diabetes, 53(4), 939–947.PubMedCrossRef Calvani, M., Scarfone, A., Granato, L., Mora, E. V., Nanni, G., Castagneto, M., et al. (2004). Restoration of adiponectin pulsatility in severely obese subjects after weight loss. Diabetes, 53(4), 939–947.PubMedCrossRef
Zurück zum Zitat Diniz, B. S., Nunes, P. V., Yassuda, M. S., Pereira, F. S., Flaks, M. K., Viola, L. F., et al. (2008). Mild cognitive impairment: Cognitive screening or neuropsychological assessment? Revista Brasileira de Psiquiatria, 30(4), 316–321.PubMedCrossRef Diniz, B. S., Nunes, P. V., Yassuda, M. S., Pereira, F. S., Flaks, M. K., Viola, L. F., et al. (2008). Mild cognitive impairment: Cognitive screening or neuropsychological assessment? Revista Brasileira de Psiquiatria, 30(4), 316–321.PubMedCrossRef
Zurück zum Zitat Diniz, B. S., Teixeira, A. L., Ojopi, E. B., Talib, L. L., Mendonca, V. A., Gattaz, W. F., et al. (2010). Higher serum sTNFR1 level predicts conversion from mild Cognitive impairment to Alzheimer’s disease. Journal of Alzheimer’s Disease, 22(4), 1305–1311. doi:10.3233/JAD-2010-100921.PubMed Diniz, B. S., Teixeira, A. L., Ojopi, E. B., Talib, L. L., Mendonca, V. A., Gattaz, W. F., et al. (2010). Higher serum sTNFR1 level predicts conversion from mild Cognitive impairment to Alzheimer’s disease. Journal of Alzheimer’s Disease, 22(4), 1305–1311. doi:10.​3233/​JAD-2010-100921.PubMed
Zurück zum Zitat Dzielinska, Z., Januszewicz, A., Wiecek, A., Demkow, M., Makowiecka-Ciesla, M., Prejbisz, A., et al. (2003). Decreased plasma concentration of a novel anti-inflammatory protein—adiponectin—in hypertensive men with coronary artery disease. Thrombosis Research, 110(5–6), 365–369.PubMedCrossRef Dzielinska, Z., Januszewicz, A., Wiecek, A., Demkow, M., Makowiecka-Ciesla, M., Prejbisz, A., et al. (2003). Decreased plasma concentration of a novel anti-inflammatory protein—adiponectin—in hypertensive men with coronary artery disease. Thrombosis Research, 110(5–6), 365–369.PubMedCrossRef
Zurück zum Zitat Fasshauer, M., Kralisch, S., Klier, M., Lossner, U., Bluher, M., Klein, J., et al. (2003). Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochemical and Biophysical Research Communications, 301(4), 1045–1050.PubMedCrossRef Fasshauer, M., Kralisch, S., Klier, M., Lossner, U., Bluher, M., Klein, J., et al. (2003). Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochemical and Biophysical Research Communications, 301(4), 1045–1050.PubMedCrossRef
Zurück zum Zitat Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189–198.PubMedCrossRef Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189–198.PubMedCrossRef
Zurück zum Zitat Forlenza, O. V., Diniz, B. S., Talib, L. L., Mendonca, V. A., Ojopi, E. B., Gattaz, W. F., et al. (2009). Increased serum IL-1beta level in Alzheimer’s disease and mild cognitive impairment. Dementia and Geriatric Cognitive Disorders, 28(6), 507–512. doi:10.1159/000255051.PubMedCrossRef Forlenza, O. V., Diniz, B. S., Talib, L. L., Mendonca, V. A., Ojopi, E. B., Gattaz, W. F., et al. (2009). Increased serum IL-1beta level in Alzheimer’s disease and mild cognitive impairment. Dementia and Geriatric Cognitive Disorders, 28(6), 507–512. doi:10.​1159/​000255051.PubMedCrossRef
Zurück zum Zitat Forlenza, O. V., Diniz, B. S., Talib, L. L., Radanovic, M., Yassuda, M. S., Ojopi, E. B., et al. (2010b). Clinical and biological predictors of Alzheimer’s disease in patients with amnestic mild cognitive impairment. Revista Brasileira de Psiquiatria, 32(3), 216–222.PubMedCrossRef Forlenza, O. V., Diniz, B. S., Talib, L. L., Radanovic, M., Yassuda, M. S., Ojopi, E. B., et al. (2010b). Clinical and biological predictors of Alzheimer’s disease in patients with amnestic mild cognitive impairment. Revista Brasileira de Psiquiatria, 32(3), 216–222.PubMedCrossRef
Zurück zum Zitat Giordano, V., Peluso, G., Iannuccelli, M., Benatti, P., Nicolai, R., & Calvani, M. (2007). Systemic and brain metabolic dysfunction as a new paradigm for approaching Alzheimer’s dementia. Neurochemistry Research, 32(4–5), 555–567. doi:10.1007/s11064-006-9125-8.CrossRef Giordano, V., Peluso, G., Iannuccelli, M., Benatti, P., Nicolai, R., & Calvani, M. (2007). Systemic and brain metabolic dysfunction as a new paradigm for approaching Alzheimer’s dementia. Neurochemistry Research, 32(4–5), 555–567. doi:10.​1007/​s11064-006-9125-8.CrossRef
Zurück zum Zitat Gu, Y., Luchsinger, J. A., Stern, Y., & Scarmeas, N. (2010). Mediterranean diet, inflammatory and metabolic biomarkers, and risk of Alzheimer’s disease. Journal of Alzheimer’s Disease, 22(2), 483–492. doi:10.3233/JAD-2010-100897.PubMed Gu, Y., Luchsinger, J. A., Stern, Y., & Scarmeas, N. (2010). Mediterranean diet, inflammatory and metabolic biomarkers, and risk of Alzheimer’s disease. Journal of Alzheimer’s Disease, 22(2), 483–492. doi:10.​3233/​JAD-2010-100897.PubMed
Zurück zum Zitat Hara, K., Horikoshi, M., Yamauchi, T., Yago, H., Miyazaki, O., Ebinuma, H., et al. (2006). Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care, 29(6), 1357–1362. doi:10.2337/dc05-1801.PubMedCrossRef Hara, K., Horikoshi, M., Yamauchi, T., Yago, H., Miyazaki, O., Ebinuma, H., et al. (2006). Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care, 29(6), 1357–1362. doi:10.​2337/​dc05-1801.PubMedCrossRef
Zurück zum Zitat Hayes, A., Thaker, U., Iwatsubo, T., Pickering-Brown, S. M., & Mann, D. M. (2002). Pathological relationships between microglial cell activity and tau and amyloid beta protein in patients with Alzheimer’s disease. Neuroscience Letters, 331(3), 171–174.PubMedCrossRef Hayes, A., Thaker, U., Iwatsubo, T., Pickering-Brown, S. M., & Mann, D. M. (2002). Pathological relationships between microglial cell activity and tau and amyloid beta protein in patients with Alzheimer’s disease. Neuroscience Letters, 331(3), 171–174.PubMedCrossRef
Zurück zum Zitat Hivert, M. F., Sullivan, L. M., Fox, C. S., Nathan, D. M., D’Agostino, R. B., Sr, Wilson, P. W., et al. (2008). Associations of adiponectin, resistin, and tumor necrosis factor-alpha with insulin resistance. The Journal of Clinical Endocrinology and Metabolism, 93(8), 3165–3172. doi:10.1210/jc.2008-0425.PubMedCrossRef Hivert, M. F., Sullivan, L. M., Fox, C. S., Nathan, D. M., D’Agostino, R. B., Sr, Wilson, P. W., et al. (2008). Associations of adiponectin, resistin, and tumor necrosis factor-alpha with insulin resistance. The Journal of Clinical Endocrinology and Metabolism, 93(8), 3165–3172. doi:10.​1210/​jc.​2008-0425.PubMedCrossRef
Zurück zum Zitat Livak, K. J. (1999). Allelic discrimination using fluorogenic probes and the 5′ nuclease assay. Genetic Analysis, 14(5–6), 143–149.PubMedCrossRef Livak, K. J. (1999). Allelic discrimination using fluorogenic probes and the 5′ nuclease assay. Genetic Analysis, 14(5–6), 143–149.PubMedCrossRef
Zurück zum Zitat Maeda, N., Shimomura, I., Kishida, K., Nishizawa, H., Matsuda, M., Nagaretani, H., et al. (2002). Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nature Medicine, 8(7), 731–737. doi:10.1038/nm724.PubMedCrossRef Maeda, N., Shimomura, I., Kishida, K., Nishizawa, H., Matsuda, M., Nagaretani, H., et al. (2002). Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nature Medicine, 8(7), 731–737. doi:10.​1038/​nm724.PubMedCrossRef
Zurück zum Zitat McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984). Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology, 34(7), 939–944.PubMedCrossRef McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984). Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology, 34(7), 939–944.PubMedCrossRef
Zurück zum Zitat Pajvani, U. B., Hawkins, M., Combs, T. P., Rajala, M. W., Doebber, T., Berger, J. P., et al. (2004). Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. Journal of Biological Chemistry, 279(13), 12152–12162. doi:10.1074/jbc.M311113200.PubMedCrossRef Pajvani, U. B., Hawkins, M., Combs, T. P., Rajala, M. W., Doebber, T., Berger, J. P., et al. (2004). Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. Journal of Biological Chemistry, 279(13), 12152–12162. doi:10.​1074/​jbc.​M311113200.PubMedCrossRef
Zurück zum Zitat Petersen, R. C., Doody, R., Kurz, A., Mohs, R. C., Morris, J. C., Rabins, P. V., et al. (2001). Current concepts in mild cognitive impairment. Archives of Neurology, 58, 1985–1992.PubMedCrossRef Petersen, R. C., Doody, R., Kurz, A., Mohs, R. C., Morris, J. C., Rabins, P. V., et al. (2001). Current concepts in mild cognitive impairment. Archives of Neurology, 58, 1985–1992.PubMedCrossRef
Zurück zum Zitat Poehlman, E. T., & Dvorak, R. V. (1998). Energy expenditure in Alzheimer’s disease. Journal of Nutrition Health and Aging, 2(2), 115–118. Poehlman, E. T., & Dvorak, R. V. (1998). Energy expenditure in Alzheimer’s disease. Journal of Nutrition Health and Aging, 2(2), 115–118.
Zurück zum Zitat Ray, S., Britschgi, M., Herbert, C., Takeda-Uchimura, Y., Boxer, A., Blennow, K., et al. (2007). Classification and prediction of clinical Alzheimer’s diagnosis based on plasma signaling proteins. Nature Medicine, 13, 1359–1362. doi:10.1038/nm1653.PubMedCrossRef Ray, S., Britschgi, M., Herbert, C., Takeda-Uchimura, Y., Boxer, A., Blennow, K., et al. (2007). Classification and prediction of clinical Alzheimer’s diagnosis based on plasma signaling proteins. Nature Medicine, 13, 1359–1362. doi:10.​1038/​nm1653.PubMedCrossRef
Zurück zum Zitat Roberts, R. O., Geda, Y. E., Knopman, D. S., Boeve, B. F., Christianson, T. J., Pankratz, V. S., et al. (2009). Association of C-reactive protein with mild cognitive impairment. Alzheimers & Dementia, 5(5), 398–405. doi:10.1016/j.jalz.2009.01.025.CrossRef Roberts, R. O., Geda, Y. E., Knopman, D. S., Boeve, B. F., Christianson, T. J., Pankratz, V. S., et al. (2009). Association of C-reactive protein with mild cognitive impairment. Alzheimers & Dementia, 5(5), 398–405. doi:10.​1016/​j.​jalz.​2009.​01.​025.CrossRef
Zurück zum Zitat Roth, M., Tym, E., Mountjoy, C. Q., Huppert, F. A., Hendrie, H., Verma, S., et al. (1986). CAMDEX. A standardised instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. British Journal of Psychiatry, 149, 698–709.PubMedCrossRef Roth, M., Tym, E., Mountjoy, C. Q., Huppert, F. A., Hendrie, H., Verma, S., et al. (1986). CAMDEX. A standardised instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. British Journal of Psychiatry, 149, 698–709.PubMedCrossRef
Zurück zum Zitat Spranger, J., Verma, S., Gohring, I., Bobbert, T., Seifert, J., Sindler, A. L., et al. (2006). Adiponectin does not cross the blood-brain barrier but modifies cytokine expression of brain endothelial cells. Diabetes, 55(1), 141–147.PubMedCrossRef Spranger, J., Verma, S., Gohring, I., Bobbert, T., Seifert, J., Sindler, A. L., et al. (2006). Adiponectin does not cross the blood-brain barrier but modifies cytokine expression of brain endothelial cells. Diabetes, 55(1), 141–147.PubMedCrossRef
Zurück zum Zitat Tarkowski, E., Andreasen, N., Tarkowski, A., & Blennow, K. (2003). Intrathecal inflammation precedes development of Alzheimer’s disease. Journal of Neurology, Neurosurgery and Psychiatry, 74, 1200–1205.CrossRef Tarkowski, E., Andreasen, N., Tarkowski, A., & Blennow, K. (2003). Intrathecal inflammation precedes development of Alzheimer’s disease. Journal of Neurology, Neurosurgery and Psychiatry, 74, 1200–1205.CrossRef
Zurück zum Zitat Taylor, V. H., & Macqueen, G. M. (2010). The role of adipokines in understanding the associations between obesity and depression. Journal of Obesity,. doi:10.1155/2010/748048. Taylor, V. H., & Macqueen, G. M. (2010). The role of adipokines in understanding the associations between obesity and depression. Journal of Obesity,. doi:10.​1155/​2010/​748048.
Zurück zum Zitat van Himbergen, T. M., Beiser, A. S., Ai, M., Seshadri, S., Otokozawa, S., Au, R., et al. (2012). Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease: Results from the Framingham Heart Study. Archives of Neurology, [Epub ahead of print]. doi:10.1001/archneurol.2011.670. van Himbergen, T. M., Beiser, A. S., Ai, M., Seshadri, S., Otokozawa, S., Au, R., et al. (2012). Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease: Results from the Framingham Heart Study. Archives of Neurology, [Epub ahead of print]. doi:10.​1001/​archneurol.​2011.​670.
Zurück zum Zitat Wolf, A. M., Wolf, D., Rumpold, H., Enrich, B., & Tilg, H. (2004). Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochemical and Biophysical Research Communications, 323(2), 630–635. doi:10.1016/j.bbrc.2004.08.145.PubMedCrossRef Wolf, A. M., Wolf, D., Rumpold, H., Enrich, B., & Tilg, H. (2004). Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochemical and Biophysical Research Communications, 323(2), 630–635. doi:10.​1016/​j.​bbrc.​2004.​08.​145.PubMedCrossRef
Zurück zum Zitat Yokota, T., Oritani, K., Takahashi, I., Ishikawa, J., Matsuyama, A., Ouchi, N., et al. (2000). Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood, 96(5), 1723–1732.PubMed Yokota, T., Oritani, K., Takahashi, I., Ishikawa, J., Matsuyama, A., Ouchi, N., et al. (2000). Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood, 96(5), 1723–1732.PubMed
Metadaten
Titel
Decreased Levels of Circulating Adiponectin in Mild Cognitive Impairment and Alzheimer’s Disease
verfasst von
Antonio L. Teixeira
Breno S. Diniz
Alline C. Campos
Aline S. Miranda
Natalia P. Rocha
Leda L. Talib
Wagner F. Gattaz
Orestes V. Forlenza
Publikationsdatum
01.03.2013
Verlag
Humana Press Inc
Erschienen in
NeuroMolecular Medicine / Ausgabe 1/2013
Print ISSN: 1535-1084
Elektronische ISSN: 1559-1174
DOI
https://doi.org/10.1007/s12017-012-8201-2

Weitere Artikel der Ausgabe 1/2013

NeuroMolecular Medicine 1/2013 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Demenzkranke durch Antipsychotika vielfach gefährdet

23.04.2024 Demenz Nachrichten

Wenn Demenzkranke aufgrund von Symptomen wie Agitation oder Aggressivität mit Antipsychotika behandelt werden, sind damit offenbar noch mehr Risiken verbunden als bislang angenommen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.