Skip to main content

Advertisement

Log in

Stage-dependent BDNF serum concentrations in Alzheimer’s disease

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary.

Alzheimer’s disease (AD) is characterized by cognitive decline and loss of neurons in specific brain regions. Recent findings have suggested an involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of AD. BDNF is an endogenous protein involved in the maintenance of neuronal function, synaptic plasticity and structural integrity in the adult brain.

To our knowledge, the present pilot study assessed for the first time BDNF serum and CSF concentrations in 30 patients with different stages of AD in comparison to 10 age-matched non-demendet controls. AD patients were divided in two groups according to their MMSE score: Group 1 (n = 15) in early stages with MMSE scores ≥21 (mean of 25.5) and Group 2 (n = 15) with more severe stages of dementia with MMSE scores <21 (mean of 13.3).

As main results, we found in patients with early stages of probable AD significantly increased BDNF serum concentrations as compared to more severe stages of AD (p < 0.0001) and age-matched healthy controls (p = 0.028). BDNF serum values in all AD patients correlated significantly with MMSE scores (r = 0.486; p < 0.0001). Levels of BDNF were below the detection limit of the assay in unconcentrated CSF samples of AD patients and non-demendet controls.

In summary, BDNF serum values are increased in early stages of Alzheimer’s disease, which may reflect a compensatory repair mechanism in early neurodegeneration and could also contribute to increased degradation of beta-amyloid (Abeta). During the course of the disease, BDNF is decreasing, which correlates with the severity of dementia. The decrease of BDNF may constitute a lack of trophic support with an increase of Abeta accumulation and thus contribute to progressive degeneration of specific regions in the AD-affected brain. BDNF should be further evaluated as a candidate marker for clinical diagnosis and therapeutic monitoring in Alzheimer’s disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • I Blasko B Grubeck-Loebenstein (2003) ArticleTitleRole of the immune system in the pathogenesis, prevention and treatment of Alzheimer’s disease Drugs Aging 20 IssueID2 101–113 Occurrence Handle12534311 Occurrence Handle1:CAS:528:DC%2BD3sXitVeqsrg%3D Occurrence Handle10.2165/00002512-200320020-00002

    Article  PubMed  CAS  Google Scholar 

  • JP Brion BH Anderton M Authelet R Dayanandan K Leroy S Lovestone JN Octave L Pradier N Touchet G Tremp (2001) ArticleTitleNeurofibrillary tangles and tau phosphorylation Biochem Soc Symp 67 81–88 Occurrence Handle11447842 Occurrence Handle1:CAS:528:DC%2BD3MXlvVygsL8%3D

    PubMed  CAS  Google Scholar 

  • GJ Burbach R Hellweg CA Haas D Del Turco U Deicke D Abramowski M Jucker M Staufenbiel T Deller (2004) ArticleTitleInduction of brain-derived neurotrophic factor in plaque-associated glial cells of aged APP23 transgenic mice J Neurosci 24 IssueID10 2421–2430 Occurrence Handle15014117 Occurrence Handle1:CAS:528:DC%2BD2cXisVKhsLc%3D Occurrence Handle10.1523/JNEUROSCI.5599-03.2004

    Article  PubMed  CAS  Google Scholar 

  • B Connor D Young P Lawlor W Gai H Waldvogel RL Faull M Dragunow (1996) ArticleTitleTrk receptor alterations in Alzheimer’s disease Brain Res Mol Brain Res 42 IssueID1 1–17 Occurrence Handle8915574 Occurrence Handle1:CAS:528:DyaK28XlvVeisrg%3D Occurrence Handle10.1016/S0169-328X(96)00040-X

    Article  PubMed  CAS  Google Scholar 

  • InstitutionalAuthorNameAPA (1994) Diagnostic and statistical manual of mental disorders EditionNumber4 DSM-4. American Psychiatric Association Washington, DC

    Google Scholar 

  • N Durany T Michel J Kurt FF Cruz-Sanchez J Cervas-Navarro P Riederer (2000) ArticleTitleBrain-derived neurotrophic factor and neurotrophin-3 levels in Alzheimer’s disease brains Int J Dev Neurosci 18 IssueID8 807–813 Occurrence Handle1:CAS:528:DC%2BD3MXitlCjsg%3D%3D Occurrence Handle10.1016/S0736-5748(00)00046-0

    Article  CAS  Google Scholar 

  • MF Folstein SE Folstein PR McHugh (1975) ArticleTitle“Mini-Mental-State”. A practical method for grading the cognitive state of patients for the clinician J Psychiatr Res 12 189–198 Occurrence Handle1202204 Occurrence Handle1:STN:280:CSmD2s7mtVE%3D Occurrence Handle10.1016/0022-3956(75)90026-6

    Article  PubMed  CAS  Google Scholar 

  • EJ Foulstone JM Tavare FJ Gunn-Moore (1999) ArticleTitleSustained phosphorylation and activation of protein kinase B correlates with brain-derived neurotrophic factor and insulin stimulated survival of cerebellar granule cells Neurosci Lett 264 IssueID1–3 125–128 Occurrence Handle10320030 Occurrence Handle1:CAS:528:DyaK1MXisFCrtbc%3D Occurrence Handle10.1016/S0304-3940(99)00166-4

    Article  PubMed  CAS  Google Scholar 

  • H Fujimura CA Altar R Chen T Nakamura T Nakahashi J Kambayashi B Sun NN Tandon (2002) ArticleTitleBrain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation Thromb Haemost 87 IssueID4 728–734 Occurrence Handle12008958 Occurrence Handle1:CAS:528:DC%2BD38Xjt1egtbs%3D

    PubMed  CAS  Google Scholar 

  • C Hock K Heese C Hulette C Rosenberg U Otten (2000) ArticleTitleRegion-specific neurotrophin imbalances in Alzheimer disease: decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas Arch Neurol 57 IssueID6 846–851 Occurrence Handle10867782 Occurrence Handle1:STN:280:DC%2BD3czivVWnsw%3D%3D Occurrence Handle10.1001/archneur.57.6.846

    Article  PubMed  CAS  Google Scholar 

  • RM Holsinger J Schnarr P Henry VT Castelo M Fahnestock (2000) ArticleTitleQuantitation of BDNF mRNA in human parietal cortex by competitive reverse transcription-polymerase chain reaction: decreased levels in Alzheimer’s disease Brain Res Mol Brain Res 76 IssueID2 347–354 Occurrence Handle10762711 Occurrence Handle1:CAS:528:DC%2BD3cXitlOlsbg%3D Occurrence Handle10.1016/S0169-328X(00)00023-1

    Article  PubMed  CAS  Google Scholar 

  • EJ Huang LF Richardt (2001) ArticleTitleNeurotrophins: roles in neuronal development and function Annu Rev Neurosci 24 677–736 Occurrence Handle11520916 Occurrence Handle1:CAS:528:DC%2BD3MXls1ShsL4%3D Occurrence Handle10.1146/annurev.neuro.24.1.677

    Article  PubMed  CAS  Google Scholar 

  • F Karege M Schwald M Cisse (2002) ArticleTitlePostnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets Neurosci Lett 328 IssueID3 261–264 Occurrence Handle12147321 Occurrence Handle1:CAS:528:DC%2BD38XlvVWitrs%3D Occurrence Handle10.1016/S0304-3940(02)00529-3

    Article  PubMed  CAS  Google Scholar 

  • M Kerschensteiner E Gallmeier L Behrens VV Leal T Misgeld WE Klinkert R Kolbeck E Hoppe RL Oropeza-Wekerle I Bartke C Stadelmann H Lassmann H Wekerle R Hohlfeld (1999) ArticleTitleActivated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation J Exp Med 189 IssueID5 865–870 Occurrence Handle10049950 Occurrence Handle1:CAS:528:DyaK1MXhsF2ju7k%3D Occurrence Handle10.1084/jem.189.5.865

    Article  PubMed  CAS  Google Scholar 

  • T Kircher H Wormstall (1997) ArticleTitleAlois Alzheimer (1864–1915) – student days and first scientific activities J Geriatr Psychiatry Neurol 10 IssueID3 127–129 Occurrence Handle9322136 Occurrence Handle1:STN:280:ByiH28zjsFY%3D

    PubMed  CAS  Google Scholar 

  • C Laske E Stransky G Eschweiler A Wittorf E Richartz-Salzburger M Bartels G Buchkremer K Schott (2005a) ArticleTitleBDNF serum concentrations in patients with Alzheimer’s disease are associated with depressive mood states Neurol Psychiatr Brain Res 12 1–4

    Google Scholar 

  • C Laske E Stransky GW Eschweiler A Wittorf E Richartz-Salzburger G Buchkremer K Schott (2005b) ArticleTitleCorrelation of BDNF and IL-6 serum concentrations in Alzheimer’s disease Neurol Psychiatr Brain Res 12 21–24

    Google Scholar 

  • C Laske C Morawetz G Buchkremer H Wormstall (2005c) ArticleTitlePrevention of dementia Dtsch Ärztebl 102 IssueID20 A1446–1453

    Google Scholar 

  • Laske C, Eschweiler GW (2006) Brain-derived neurotrophic factor (BDNF): from nerve growth factor to modulator of brain plasticity in cognitive processes and psychiatric diseases. Nervenarzt (in press)

  • O Lindvall P Ernfors J Bengzon Z Kokaia ML Smith BK Siesjo H Persson (1992) ArticleTitleDifferential regulation of mRNAs for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the adult rat brain following cerebral ischemia and hypoglycemic coma Proc Natl Acad Sci USA 89 648–652 Occurrence Handle1731336 Occurrence Handle1:CAS:528:DyaK38XhtVeks7Y%3D Occurrence Handle10.1073/pnas.89.2.648

    Article  PubMed  CAS  Google Scholar 

  • F Marmigere C Choby F Rage S Richard L Tapia-Arancibia (2001) ArticleTitleRapid stimulatory effects of brain-derived neurotrophic factor and neurotrophin-3 on somatostatin release and intracellular calcium rise in primary hypothalamic cell cultures Neuroendocrinology 74 IssueID1 43–54 Occurrence Handle11435757 Occurrence Handle1:CAS:528:DC%2BD3MXlsVeit7c%3D Occurrence Handle10.1159/000054669

    Article  PubMed  CAS  Google Scholar 

  • MP Mattson S Maudsley B Martin (2004) ArticleTitleBDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders Trends Neurosci 27 589–594 Occurrence Handle15374669 Occurrence Handle1:CAS:528:DC%2BD2cXnslOjtrs%3D Occurrence Handle10.1016/j.tins.2004.08.001

    Article  PubMed  CAS  Google Scholar 

  • G Mc Khann D Drachman M Folstein R Katzman D Price EM Stadlan (1984) ArticleTitleClinical 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 30–44

    Google Scholar 

  • L Meda MA Cassatella GI Szendrei L Otvos P Baron M Villalba D Ferrari F Rossi (1995) ArticleTitleActivation of microglial cells by beta-amyloid protein and interferon-gamma Nature 374 647–651 Occurrence Handle7715705 Occurrence Handle1:CAS:528:DyaK2MXltVOhsLs%3D Occurrence Handle10.1038/374647a0

    Article  PubMed  CAS  Google Scholar 

  • B Michalski M Fahnestock (2003) ArticleTitlePro-brain-derived neurotrophic factor is decreased in parietal cortex in Alzheimer’s disease Brain Res Mol Brain Res 111 IssueID1–2 148–154 Occurrence Handle12654514 Occurrence Handle1:CAS:528:DC%2BD3sXitlWrt7w%3D Occurrence Handle10.1016/S0169-328X(03)00003-2

    Article  PubMed  CAS  Google Scholar 

  • W Pan WA Banks MB Fasold J Bluth AJ Kastin (1998) ArticleTitleTransport of brain-derived neurotrophic factor across the blood-brain barrier Neuropharmacology 37 IssueID12 1553–1561 Occurrence Handle9886678 Occurrence Handle1:CAS:528:DyaK1MXisFensQ%3D%3D Occurrence Handle10.1016/S0028-3908(98)00141-5

    Article  PubMed  CAS  Google Scholar 

  • HS Phillips JM Hains M Armanini GR Laramee SA Johnson JW Winslow (1991) ArticleTitleBDNF mRNA is decreased in the hippocampus of individuals with Alzheimer’s disease Neuron 7 IssueID5 695–702 Occurrence Handle1742020 Occurrence Handle1:CAS:528:DyaK38Xht1KisLo%3D Occurrence Handle10.1016/0896-6273(91)90273-3

    Article  PubMed  CAS  Google Scholar 

  • JF Poduslo GL Curran (1996) ArticleTitlePermeability at the blood-brain barrier and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF Mol Brain Res 36 280–286 Occurrence Handle8965648 Occurrence Handle1:CAS:528:DyaK28XhvVKrtbs%3D Occurrence Handle10.1016/0169-328X(95)00250-V

    Article  PubMed  CAS  Google Scholar 

  • T Saito N Iwata S Tsubuki Y Takaki J Takano SM Huang T Suemoto M Higuchi TC Saido (2005) ArticleTitleSomatostatin regulates brain amyloid beta peptide Abeta42 through modulation of proteolytic degradation Nat Med 11 IssueID4 434–439 Occurrence Handle15778722 Occurrence Handle1:CAS:528:DC%2BD2MXivFCgsrs%3D Occurrence Handle10.1038/nm1206

    Article  PubMed  CAS  Google Scholar 

  • Y Tang K Yamada Y Kanou T Miyazaki X Xiong F Kambe Y Murata H Seo T Nabeshima (2000) ArticleTitleSpatiotemporal expression of BDNF in the hippocampus induced by the continuous intracerebroventricular infusion of beta-amyloid in rats Brain Res Mol Brain 80 IssueID2 188–197 Occurrence Handle1:CAS:528:DC%2BD3cXmtF2qsbc%3D Occurrence Handle10.1016/S0169-328X(00)00158-3

    Article  CAS  Google Scholar 

  • L Tong R Balazs PL Thornton CW Cotman (2004) ArticleTitleBeta-amyloid peptide at sublethal concentrations downregulates brain-derived neurotrophic factor functions in cultured cortical neurons J Neurosci 24 IssueID30 6799–6809 Occurrence Handle15282285 Occurrence Handle1:CAS:528:DC%2BD2cXmsVCktr8%3D Occurrence Handle10.1523/JNEUROSCI.5463-03.2004

    Article  PubMed  CAS  Google Scholar 

  • G Villuendas F Sanchez-Franco N Palacios M Fernandez L Cacicedo (2001) ArticleTitleInvolvement of VIP on BDNF-induced somatostatin gene expression in cultured fetal rat cerebral cortical cells Brain Res Mol Brain Res 94 IssueID1–2 59–66 Occurrence Handle11597765 Occurrence Handle1:CAS:528:DC%2BD3MXnsVSnt70%3D Occurrence Handle10.1016/S0169-328X(01)00177-2

    Article  PubMed  CAS  Google Scholar 

  • World Health Organization (WHO) (1988) Tenth revision of the International Classification of Diseases, chapter 5 (F). Mental and behavioural disorders (including disorders of psychological development). Clinical descriptions and diagnostic guidelines. WHO, Geneva

  • C Yasutake T Yanagawa T Okamura H Yoneda (2005) ArticleTitleSerum BDNF, TNF-alpha, IL-1beta levels in dementia patients World J Biol Psychiatry 6 IssueID[Suppl 1] 215

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Laske, C., Stransky, E., Leyhe, T. et al. Stage-dependent BDNF serum concentrations in Alzheimer’s disease. J Neural Transm 113, 1217–1224 (2006). https://doi.org/10.1007/s00702-005-0397-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-005-0397-y

Navigation