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Investigation of the Molecular Role of Brain-Derived Neurotrophic Factor in Alzheimer’s Disease

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Abstract

Brain-derived neurotrophic factor (BDNF), or abrineurin, is a member of the neurotrophin family of growth factors that acts on both the central and peripheral nervous systems. BDNF is also well known for its cardinal role in normal neural maturation. It binds to at least two receptors at the cell surface known as tyrosine kinase B (TrkB) and p75NTR. Additional neurotrophins that are anatomically linked with BDNF include neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), and nerve growth factor (NGF). It is evident that BDNF levels in patients with Alzheimer’s disease (AD) are altered. AD is a progressive disorder and a form of dementia, where the mental function of an elderly person is disrupted. It is associated with a progressive decline in cognitive function, which mainly targets the thinking, memory, and behavior of the person. The degeneration of neurons occurs in the cerebral cortex region of brain. The two major sources responsible for neuronal degeneration are protein fragment amyloid-beta (Aβ), which builds up in the spaces between the nerve cells, known as plaques, disrupting the neuron signaling pathway and leading to dementia, and neurofibrillary tangles (NFTs), which are the twisted fibers of proteins that build up inside the cells. AD is highly prevalent, with recent data indicating nearly 5.8 million Americans aged 65 and older with AD in 2020, and with 80% of patients 75 and older. AD is recognized as the sixth leading cause of death in the USA, and its prevalence is predicted to increase exponentially in the coming years. As AD worsens over time, it becomes increasingly important to understand the exact pathophysiology, biomarkers, and treatment. In this article, we focus primarily on the controversial aspect of BDNF in AD, including its influence on various other proteins and enzymes and the current treatments associated with BDNF, along with future perspectives.

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Abbreviations

Aβ :

Amyloid Beta

AD :

Alzheimer’s disease

APP :

Amyloid precursor protein

BDNF :

Brain-derived neurotrophic factor

NFTs :

Neurofibrillary tangles

NGFs:

Nerve growth factors

TrkB :

Tyrosine kinase B

References

  1. Jiao SS, Shen LL, Zhu C et al (2016) Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer’s disease. Transl Psychiatry. 6(10):e907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ye X, Tai W, Zhang D (2012) The early events of Alzheimer’s disease pathology: from mitochondrial dysfunction to BDNF axonal transport deficits. Neurobiol Aging. 33(6):1122-e1

    Article  PubMed  Google Scholar 

  3. Herrmann N, Chau SA, Kircanski I, Lanctot KL (2011) Current and emerging drug treatment options for Alzheimer’s disease. Drugs. 71(15):2031–65

    Article  CAS  PubMed  Google Scholar 

  4. Wang ZH, Xiang J, Liu X et al (2019) Deficiency in BDNF/TrkB Neurotrophic Activity Stimulates δ-Secretase by Upregulating C/EBPβ in Alzheimer’s Disease. Cell Rep. 28(3):655–69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ninan I (2014) Synaptic regulation of affective behaviors; role of BDNF. Neuropharmacology. 1(76):684–95

    Article  Google Scholar 

  6. Cattaneo A, Cattane N, Begni V, Pariante CM, Riva MA (2016) The human BDNF gene: peripheral gene expression and protein levels as biomarkers for psychiatric disorders. Transl Psychiatry. 6(11):e958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Autry AE, Monteggia LM (2012) Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev. 64(2):238–58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Genius J, Klafki H, Benninghoff J, Esselmann H, Wiltfang J (2012) Current application of neurochemical biomarkers in the prediction and differential diagnosis of Alzheimer’s disease and other neurodegenerative dementias. Eur Arch Psychiatry Clin Neurosci. 262(2):71–7

    Article  Google Scholar 

  9. Fu L, Doreswamy V, Prakash R (2014) The biochemical pathways of central nervous system neural degeneration in niacin deficiency. Neural Regen Res. 9(16):1509

    Article  PubMed  PubMed Central  Google Scholar 

  10. Denham J, Marques FZ, O’Brien BJ, Charchar FJ (2014) Exercise: putting action into our epigenome. Sports Med. 44(2):189–209

    Article  PubMed  Google Scholar 

  11. Szuhany KL, Bugatti M, Otto MW (2015) A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. J Psychiatric Res. 1(60):56–64

    Article  Google Scholar 

  12. Bachurin SO, Bovina EV, Ustyugov AA (2017) Drugs in clinical trials for Alzheimer’s disease: the major trends. Med Res Rev. 37(5):1189–225

    Article  Google Scholar 

  13. Broadstock M, Ballard C, Corbett A (2014) Latest treatment options for Alzheimer’s disease, Parkinson’s disease dementia and dementia with Lewy bodies. Expert Opin Pharmacother. 15(13):1797–810

    Article  CAS  PubMed  Google Scholar 

  14. Karch CM, Goate AM (2015) Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry. 77(1):43–51

    Article  CAS  PubMed  Google Scholar 

  15. Chen X, Yan SD (2006) Mitochondrial Aβ A potential cause of metabolic dysfunction in Alzheimer’s disease. IUBMB Life. 58(12):686–94

    Article  CAS  PubMed  Google Scholar 

  16. Kang JE, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR et al (2009) Amyloid-β dynamics are regulated by orexin and the sleep-wake cycle. Science. 326(5955):1005–7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M et al (2013) Sleep drives metabolite clearance from the adult brain. Science. 342(6156):373–7

    Article  CAS  PubMed  Google Scholar 

  18. Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C et al (2013) Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nature Genet. 45(12):1452–8

    Article  CAS  PubMed  Google Scholar 

  19. Waring SC, Rosenberg RN (2008) Genome-Wide Association Studies in Alzheimer Disease. Arch Neurol. 65(3):329–34

    Article  PubMed  Google Scholar 

  20. Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL et al (2015) Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 14(4):388–405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Karch CM, Goate AM (2015) Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry. 77(1):43–51

    Article  CAS  PubMed  Google Scholar 

  22. Hickman SE, El Khoury J (2014) TREM2 and the neuroimmunology of Alzheimer's disease. Biochem Pharmacol 88(4):495–8

  23. Katsumoto A, Takeuchi H, Takahashi K, Tanaka F (2018) Microglia in Alzheimer’s disease: risk factors and inflammation. Front Neurol. 15(9):978

    Article  Google Scholar 

  24. Guerreiro R, Wojtas A, Bras JC, Carrasquillo M, Rogaeva E, Majounie E et al (2013) TREM2 deficiency alters acute macrophage distribution and improves recovery after TBI. N Engl J Med 117–27

  25. Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E (2011) Alzheimer’s disease. Lancet (London, England). 377(9770):1091–31

    Article  Google Scholar 

  26. Kowiański P, Lietzau G, Czuba E, Waśkow M, Steliga A, Moryś J (2018) BDNF: a key factor with multipotent impact on brain signaling and synaptic plasticity. Cell Mol Neurobiol. 38(3):579–93

    Article  PubMed  Google Scholar 

  27. Mandel AL, Ozdener H, Utermohlen V (2009) Identification of pro-and mature brain-derived neurotrophic factor in human saliva. Arch Oral Biol 54(7):689–95

  28. Qiu LL, Pan W, Luo D et al (2020) Dysregulation of BDNF/TrkB signaling mediated by NMDAR/Ca 2+/calpain might contribute to postoperative cognitive dysfunction in aging mice. J Neuroinflammation. 17(1):1–5

    Article  Google Scholar 

  29. Zheng F, Wang H (2009) NMDA-mediated and self-induced bdnf exon IV transcriptions are differentially regulated in cultured cortical neurons. Neurochem Int. 54(5–6):385–92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Yamada K, Nabeshima T (2003) Brain-derived neurotrophic factor/TrkB signaling in memory processes. J Pharm Sci. 91(4):267–70

    Article  CAS  Google Scholar 

  31. Bath KG, Lee FS (2006) Variant BDNF (Val66Met) impact on brain structure and function. Cogn Affect Behav Neurosci. 6(1):79–85

    Article  PubMed  Google Scholar 

  32. Lu B, Nagappan G, Guan X, Nathan PJ, Wren P (2013) BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases. Nat Rev Neurosci. 14(6):401–16

    Article  CAS  PubMed  Google Scholar 

  33. Tsai SJ, Hong CJ, Liu HC, Liu TY, Hsu LE, Lin CH (2004) Association analysis of brain-derived neurotrophic factor Val66Met polymorphisms with Alzheimer’s disease and age of onset. Neuropsychobiology. 49(1):10–2

    Article  CAS  PubMed  Google Scholar 

  34. Tsai SJ, Hong CJ, Liu HC, Liu TY, Liou YJ (2006) The brain-derived neurotrophic factor gene as a possible susceptibility candidate for Alzheimer’s disease in a chinese population. Dement Geriatr Cogn Disord. 21(3):139–43

    Article  CAS  PubMed  Google Scholar 

  35. Amidfar M, de Oliveira J, Kucharska E, Budni J, Kim YK (2020) CREB and BDNF: Neurobiology and treatment of Alzheimer’s disease. Life Sci. 27:118020

    Article  Google Scholar 

  36. Tejeda GS, Díaz-Guerra M (2017) Integral characterization of defective BDNF/TrkB signalling in neurological and psychiatric disorders leads the way to new therapies. Int J Mol Sci. 18(2):268

    Article  PubMed Central  Google Scholar 

  37. Fahnestock M, Garzon D, Holsinger RM, Michalski B (2002) Neurotrophic factors and Alzheimer’s disease: are we focusing on the wrong molecule? In Ageing and Dementia Current and Future Concepts. Springer, Vienna, pp 241–252

    Google Scholar 

  38. Peng S, Wuu J, Mufson EJ, Fahnestock M (2005) Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer’s disease. J Neurochem. 93(6):1412–21

    Article  CAS  PubMed  Google Scholar 

  39. Wu CC, Lien CC, Hou WH, Chiang PM, Tsai KJ (2016) Gain of BDNF function in engrafted neural stem cells promotes the therapeutic potential for Alzheimer’s disease. Sci Rep 6(27358)

  40. Mitchelmore C, Gede L (2014) Brain derived neurotrophic factor: epigenetic regulation in psychiatric disorders. Brain Res. 24(162–72):1586

    Google Scholar 

  41. Pramanik S, Sulistio YA, Heese K (2017) Neurotrophin signalling and stem cells-implications for neurodegenerative diseases and stem cell therapy. Mol Biol. 54(9):7401–59

    CAS  Google Scholar 

  42. Kao PF, Banigan MG, Vanderburg CR et al (2012) Increased expression of TrkB and Capzb2 accompanies preserved cognitive status in early Alzheimer disease pathology. J Neuropathy Exp Neurol 71(7):654–64

  43. Weinstein G, Beiser AS, Choi SH et al (2014) Serum brain-derived neurotrophic factor and the risk for dementia: the Framingham Heart Study. JAMA Neurol 71(1):55–61

  44. Bitner RS (2012) Cyclic AMP response element-binding protein (CREB) phosphorylation: a mechanistic marker in the development of memory enhancing Alzheimer’s disease therapeutics. Biochem Pharmacol. 83(6):705–14

    Article  Google Scholar 

  45. Hu YS, Long N, Pigino G, Brady ST, Lazarov O (2013) Molecular mechanisms of environmental enrichment: impairments in Akt/GSK3β, neurotrophin-3 and CREB signaling. PloS One. 8(5):e64460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Pláteník J, Fišar Z, Buchal R et al (2014) GSK3β, CREB, and BDNF in peripheral blood of patients with Alzheimer’s disease and depression. Prog Neuro-Psychopharmacol Biol Psychiatry. 3(50):83–93

    Article  Google Scholar 

  47. Yoshii A, Constantine-Paton M (2010) Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease. Dev Neurobiol. 70(5):304–22

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Zhang F, Kang Z, Li W, Xiao Z, Zhou X (2012) Roles of brain-derived neurotrophic factor/tropomyosin-related kinase B (BDNF/TrkB) signalling in Alzheimer’s disease. J Clin Neurosci. 19(7):946–9

    Article  CAS  PubMed  Google Scholar 

  49. Chen Q, Zhou Z, Zhang L et al (2012) Tau protein is involved in morphological plasticity in hippocampal neurons in response to BDNF. Neurochem Int. 60(3):233–42

    Article  CAS  PubMed  Google Scholar 

  50. Rosa E, Mahendram S, Ke YD, Ittner LM, Ginsberg SD, Fahnestock M (2016) Tau downregulates BDNF expression in animal and cellular models of Alzheimer's disease. Neurobiol Aging 135–42

  51. Davis J, Maes M, Andreazza A, McGrath JJ, Tye SJ, Berk M (2015) Towards a classification of biomarkers of neuropsychiatric disease: from encompass to compass. Mol Psychiatry. 20(2):152–3

    Article  CAS  PubMed  Google Scholar 

  52. Pillai A, Buckley PF (2012) Reliable biomarkers and predictors of schizophrenia and its treatment. Psychiatric Clin. 35(3):645–59

    Google Scholar 

  53. O’Bryant SE, Hobson VL, Hall JR et al (2011) Serum brain-derived neurotrophic factor levels are specifically associated with memory performance among Alzheimer’s disease cases. Dement Geriatr Cogn Disord. 31(6):31–6

    Article  PubMed  Google Scholar 

  54. Angelucci F, Spalletta G, Iulio FD et al (2010) Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI) patients are characterized by increased BDNF serum levels. Curr Alzheimer Res. 7(1):15–20

    Article  CAS  PubMed  Google Scholar 

  55. Laske C, Stransky E, Leyhe T et al (2006) Stage-dependent BDNF serum concentrations in Alzheimer’s disease. J Neural Transm. 113(9):1217–24

    Article  CAS  PubMed  Google Scholar 

  56. Winblad B, Palmer K, Kivipelto M et al (2004) Mild cognitive impairment–beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med. 256(3):240–6

    Article  CAS  PubMed  Google Scholar 

  57. Gezen-Ak D, Dursun E, Hanağası H et al (2013) BDNF, TNFα, HSP90, CFH, and IL-10 serum levels in patients with early or late onset Alzheimer’s disease or mild cognitive impairment. J Alzheimer’s Dis. 37(1):185–95

    Article  CAS  Google Scholar 

  58. O’Bryant SE, Hobson V, Hall JR et al (2009) Brain-derived neurotrophic factor levels in Alzheimer’s disease. J Alzheimer’s Dis. 17(2):337–41

    Article  CAS  Google Scholar 

  59. Buchman AS, Yu L, Boyle PA, Schneider JA, De Jager PL, Bennett DA (2016) Higher brain BDNF gene expression is associated with slower cognitive decline in older adults. Neurology. 86(8):735–41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Balietti M (2020) Blood brain-derived neurotrophic factor as a biomarker of Alzheimer's disease. In Diagnosis and Management in Dementia. Academic Press: 281–296

  61. Diniz BS, Teixeira AL (2011) Brain-derived neurotrophic factor and Alzheimer’s disease: physiopathology and beyond. Neuromol Med. 13(4):217–22

    Article  CAS  Google Scholar 

  62. Gylys KH, Fein JA, Yang F, Wiley DJ, Miller CA, Cole GM (2004) Synaptic changes in Alzheimer’s disease: increased amyloid-β and gliosis in surviving terminals is accompanied by decreased PSD-95 fluorescence. Am J Pathol. 165(5):1809–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lee L, Dale E, Staniszewski A et al (2014) Regulation of synaptic plasticity and cognition by SUMO in normal physiology and Alzheimer’s disease. Sci Rep. 2(4):7190

    Article  Google Scholar 

  64. Matsuzaki M, Honkura N, Ellis-Davies GC, Kasai H (2004) Structural basis of long-term potentiation in single dendritic spines. Nature. 429(6993):761–6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. McDole B, Isgor C, Pare C, Guthrie K (2015) BDNF over-expression increases olfactory bulb granule cell dendritic spine density in vivo. Neuroscience. 24(304):146–60

    Article  Google Scholar 

  66. Somers C, Struyfs H, Goossens J, Niemantsverdriet E, Luyckx J, De Roeck N et al (2016) A decade of cerebrospinal fluid biomarkers for Alzheimer’s disease in Belgium. J Alzheimer’s Dis. 54(1):383–95

    Article  CAS  Google Scholar 

  67. Goossens J, Bjerke M, Struyfs H, Niemantsverdriet E, Somers C, Van den Bossche T et al (2017) No added diagnostic value of non-phosphorylated tau fraction (p-tau rel) in CSF as a biomarker for differential dementia diagnosis. Alzheimer’s Res Ther. 9(1):1–7

    Article  Google Scholar 

  68. Anoop A, Singh PK, Jacob RS, Maji SK (2010) CSF biomarkers for Alzheimer’s disease diagnosis. Int J Alzheimer’s Dis. 23:2010

    Google Scholar 

  69. Blennow K, Hampel H, Weiner M, Zetterberg H (2010) Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol. 6(3):131–44

    Article  CAS  PubMed  Google Scholar 

  70. Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L (2006) Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 5(3):228–34

    Article  CAS  PubMed  Google Scholar 

  71. Zetterberg H (2006) Neurological Biomarkers. Rev Cell Biol Mol Med. 2(1):62–75

    Google Scholar 

  72. Welge V, Fiege O, Lewczuk P, Mollenhauer B, Esselmann H, Klafki HW et al (2009) Combined CSF tau, p-tau181 and amyloid-β 38/40/42 for diagnosing Alzheimer’s disease. J Neural Transm. 1(11):203–12

    Article  Google Scholar 

  73. Miranda M, Morici JF, Zanoni MB, Bekinschtein P (2019) Brain-derived neurotrophic factor: a key molecule for memory in the healthy and the pathological brain. Front Cell Neurosci. 13:363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Hsiao YH, Hung HC, Chen SH, Gean PW (2014) Social interaction rescues memory deficit in an animal model of Alzheimer’s disease by increasing BDNF-dependent hippocampal neurogenesis. J Neurosci. 34(49):16207–19

    Article  PubMed  PubMed Central  Google Scholar 

  75. Han K, Jia N, Li J, Yang L, Min LQ (2013) Chronic caffeine treatment reverses memory impairment and the expression of brain BNDF and TrkB in the PS1/APP double transgenic mouse model of Alzheimer’s disease. Mol Med Rep. 8(3):737–40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Prakash A, Kumar A (2014) Role of nuclear receptor on regulation of BDNF and neuroinflammation in hippocampus of β-amyloid animal model of Alzheimer’s disease. Neurotox Res. 25(4):335–47

    Article  CAS  PubMed  Google Scholar 

  77. Fukumoto K, Mizoguchi H, Takeuchi H et al (2014) Fingolimod increases brain-derived neurotrophic factor levels and ameliorates amyloid β-induced memory impairment. Behav Brain Res. 15(268):88–93

    Article  Google Scholar 

  78. Budni J, Bellettini-Santos T, Mina F, Garcez ML, Zugno AI (2015) The involvement of BDNF, NGF and GDNF in aging and Alzheimer’s disease. Aging Dis. 6(5):331

    Article  PubMed  PubMed Central  Google Scholar 

  79. Géral C, Angelova A, Lesieur S (2013) From molecular to nanotechnology strategies for delivery of neurotrophins: emphasis on brain-derived neurotrophic factor (BDNF). Pharmaceutics. 5(1):127–67

    Article  PubMed  PubMed Central  Google Scholar 

  80. Wahlberg LU, Lind G, Almqvist PM, Kusk P, Tornøe J, Juliusson B, Söderman M, Selldén E, Seiger Å, Eriksdotter-Jönhagen M, Linderoth B (2012) Targeted delivery of nerve growth factor via encapsulated cell biodelivery in Alzheimer disease: a technology platform for restorative neurosurgery. J Neurosurg. 117(2):340–7

    Article  PubMed  Google Scholar 

  81. Lu P, Jones LL, Tuszynski MH (2005) BDNF-expressing marrow stromal cells support extensive axonal growth at sites of spinal cord injury. Exp Neurol. 191(2):344–60

    Article  CAS  PubMed  Google Scholar 

  82. Lu KW, Chen ZY, Jin DD, Hou TS, Cao L, Fu Q (2002) Cationic liposome-mediated GDNF gene transfer after spinal cord injury. J Neurotrauma. 19(9):1081–90

    Article  PubMed  Google Scholar 

  83. Leyhe T, Stransky E, Eschweiler GW, Buchkremer G, Laske C (2008) Increase of BDNF serum concentration during donepezil treatment of patients with early Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci. 258(2):124–8

    Article  CAS  PubMed  Google Scholar 

  84. Polyakova M, Stuke K, Schuemberg K, Mueller K, Schoenknecht P, Schroeter ML (2015) BDNF as a biomarker for successful treatment of mood disorders: a systematic & quantitative meta-analysis. J Affect Disord. 15(174):432–40

    Article  Google Scholar 

  85. Song JH, Yu JT, Tan L (2015) Brain-derived neurotrophic factor in Alzheimer’s disease: risk, mechanisms, and therapy. Mol Neurobiol. 52(3):1477–93

    Article  CAS  PubMed  Google Scholar 

  86. Autio H, Mätlik K, Rantamäki T et al (2011) Acetylcholinesterase inhibitors rapidly activate Trk neurotrophin receptors in the mouse hippocampus. Neuropharmacology. 61(8):1291–6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Ventriglia M, Zanardini R, Bonomini C, Zanetti O, Volpe D, Pasqualetti P et al (2013) Serum brain-derived neurotrophic factor levels in different neurological diseases. BioMed Res Int

  88. Huang TL, Hung YY (2009) Lorazepam reduces the serum brain-derived neurotrophic factor level in schizophrenia patients with catatonia. Prog Neuropsychopharmacol Biol Psychiatry. 1(33):158–9

    Article  Google Scholar 

  89. Balietti M, Giuli C, Conti F (2018) Peripheral blood brain-derived neurotrophic factor as a biomarker of Alzheimer’s disease: are there methodological biases? Mol Neurobiol. 55(8):6661–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Sakr HF, Khalil KI, Hussein AM, Zaki MS, Eid RA, Alkhateeb M (2014) Effect of dehydroepiandrosterone (DHEA) on memory and brain derived neurotrophic factor (BDNF) in a rat model of vascular dementia. J Physiol Pharmacol. 65(1):41–53

    CAS  PubMed  Google Scholar 

  91. Watanabe K, Hashimoto E, Ukai W et al (2010) Effect of antidepressants on brain-derived neurotrophic factor (BDNF) release from platelets in the rats. Prog Neuro-Psychopharmacol Biol Psychiatry. 34(8):1450–4

    Article  CAS  Google Scholar 

  92. Calabrese F, Luoni A, Guidotti G, Racagni G, Fumagalli F, Riva MA (2013) Modulation of neuronal plasticity following chronic concomitant administration of the novel antipsychotic lurasidone with the mood stabilizer valproic acid. Psychopharmacology. 226(1):101–12

    Article  CAS  PubMed  Google Scholar 

  93. Martisova E, Aisa B, Guereñu G, Javier Ramirez M (2013) Effects of early maternal separation on biobehavioral and neuropathological markers of Alzheimer’s disease in adult male rats. Curr Alzheimer Res. 10(4):420–32

    Article  CAS  PubMed  Google Scholar 

  94. Weinstein G, R Preis S, S Beiser A et al (2017) Clinical and environmental correlates of serum BDNF: a descriptive study with plausible implications for AD research. Curr Alzheimer Res 14(7):722–30

  95. Zhang J, Mu X, Breker DA, Li Y, Gao Z, Huang Y (2017) Atorvastatin treatment is associated with increased BDNF level and improved functional recovery after atherothrombotic stroke. Int J Neurosci. 127(1):92–7

    Article  CAS  PubMed  Google Scholar 

  96. Allard JS, Perez EJ, Fukui K, Carpenter P, Ingram DK, de Cabo R (2016) Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL/6J mice. Behav Brain Res. 15(301):1–9

    Article  Google Scholar 

  97. Nagahara AH, Merrill DA, Coppola G et al (2009) Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease. Nat Med. 15(3):331–7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Begley DJ (2004) Delivery of therapeutic agents to the central nervous system: the problems and the possibilities. Pharmacol Ther. 104(1):29–45

    Article  CAS  PubMed  Google Scholar 

  99. Craparo EF, Bondì ML, Pitarresi G, Cavallaro G (2011) Nanoparticulate systems for drug delivery and targeting to the central nervous system. CNS Neurosci Ther. 17(6):670–7

    Article  CAS  PubMed  Google Scholar 

  100. Petros RA, DeSimone JM (2010) Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discov. 9(8):615–27

    Article  CAS  PubMed  Google Scholar 

  101. Zhang S, Uludağ H (2009) Nanoparticulate systems for growth factor delivery. Pharmaceutical research. 26(7):1561

    Article  CAS  PubMed  Google Scholar 

  102. Xie Y, Ye L, Zhang X, Cui W, Lou J, Nagai T, Hou X (2005) Transport of nerve growth factor encapsulated into liposomes across the blood–brain barrier: in vitro and in vivo studies. J Control Release. 105(1–2):106–19

    Article  CAS  PubMed  Google Scholar 

  103. Pang Z, Lu W, Gao H, Hu K, Chen J, Zhang C, Gao X, Jiang X, Zhu C (2008) Preparation and brain delivery property of biodegradable polymersomes conjugated with OX26. J Control Release. 128(2):120–7

    Article  CAS  PubMed  Google Scholar 

  104. Glasky AJ, Melchior CL, Pirzadeh B, Heydari N, Ritzmann RF (1994) Effect of AIT-082, a purine analog, on working memory in normal and aged mice. Pharmacol Biochem Behav. 47(2):325–9

    Article  CAS  PubMed  Google Scholar 

  105. Devi L, Ohno M (2012) 7, 8-dihydroxyflavone, a small-molecule TrkB agonist, reverses memory deficits and BACE1 elevation in a mouse model of Alzheimer’s disease. Neuropsychopharmacology. 37(2):434–44

    Article  CAS  PubMed  Google Scholar 

  106. Shin MK, Kim HG, Baek SH et al (2014) Neuropep-1 ameliorates learning and memory deficits in an Alzheimer’s disease mouse model, increases brain-derived neurotrophic factor expression in the brain, and causes reduction of amyloid beta plaques. Neurobiol Aging. 35(5):990–1001

    Article  CAS  PubMed  Google Scholar 

  107. Chen C, Wang Z, Zhang Z et al (2018) The prodrug of 7, 8-dihydroxyflavone development and therapeutic efficacy for treating Alzheimer’s disease. Proc Natl Acad Sci. 115(3):578–83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Shin MK, Kim HG, Kim KL (2011) A novel trimeric peptide, Neuropep-1-stimulating brain-derived neurotrophic factor expression in rat brain improves spatial learning and memory as measured by the Y-maze and Morris water maze. J Neurochem. 116(2):205–16

    Article  CAS  PubMed  Google Scholar 

  109. Vaynman S, Ying Z, Gomez-Pinilla F (2004) Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci. 20(10):2580–90

    Article  PubMed  Google Scholar 

  110. Ng TK, Ho CS, Tam WW, Kua EH, Ho RC (2019) Decreased serum brain-derived neurotrophic factor (BDNF) levels in patients with Alzheimer’s disease (AD): a systematic review and meta-analysis. Int J Mol Sci. 20(2):257

    Article  PubMed Central  Google Scholar 

  111. Ubhi K, Masliah E (2013) Alzheimer’s disease: recent advances and future perspectives. J Alzheimer’s Dis. 33(s1):S185-94

    Article  Google Scholar 

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Acknowledgements

The authors would like to thank Chitkara College of Pharmacy, Chitkara University, Punjab, India for providing the basic facilities for completion of the current article.

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The present review article did not receive any funding.

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P.G. and T.B.: Conceived the idea and wrote the first draft; A.S.: Figure work; S.S.: Data compilation; S.B.: Proofreading.

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Correspondence to Tapan Behl.

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Girotra, P., Behl, T., Sehgal, A. et al. Investigation of the Molecular Role of Brain-Derived Neurotrophic Factor in Alzheimer’s Disease. J Mol Neurosci 72, 173–186 (2022). https://doi.org/10.1007/s12031-021-01824-8

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