Consequence of Dementia and Cognitive Impairment by Primary Nucleation Pathway

Abstract

An acquired loss of cognition in several cognitive domains that is severe enough to interfere with social or professional functioning is called dementia. As well as a moderately in-depth mental status examination by a clinician to identify impairments in memory, language, attention, visuospatial cognition, such as spatial orientation, executive function, and mood, the diagnosis of dementia requires a history evaluating for cognitive decline and impairment in daily activities, with confirmation from a close friend or family member. The start and organization of the cognitive assessment can be helped by short screening tests for cognitive impairment. Clinical presentations show that neurodegenerative diseases are often incurable because patients permanently lose some types of neurons. It has been determined through an assessment that, at best, our understanding of the underlying processes is still rudimentary, which presents exciting new targets for further study as well as the development of diagnostics and drugs. A growing body of research suggests that they also advance our knowledge of the processes that are probably crucial for maintaining the health and functionality of the brain. We concentrate on a number of the animal models of memory problems that have been mentioned in this review article because dementia has numerous etiologies. Serious neurological impairment and neuronal death are the main features of neurodegenerative illnesses, which are also extremely crippling ailments. The most prevalent neurodegenerative disorders are followed by those primary nucleation pathways responsible for cognitive impairment and dementia.

Key words

norepinephrine - adrenal - steroid hormones - serotonin - neuroendocrine - neuropeptides

Publikationsverlauf

Eingereicht: 02. Januar 2023

Angenommen nach Revision: 02. März 2023

Artikel online veröffentlicht:
02. Mai 2023

• References

• 1 Yang H, Chen J, Tang S. et al. New drug R&D of traditional Chinese medicine: role of data mining approaches. J Biol Syst 2009; 17: 329-347
• 2 Xie L, Li J, Xie L. et al. Drug discovery using chemical systems biology: identification of the protein-ligand binding network to explain the side effects of CETP inhibitors. PLoS Comput Biol 2009; 5: e1000387
• 3 Goh KI, Cusick ME, Valle D. et al. The human disease network. Proc Natl Acad Sci 2007; 104: 8685-8690
• 4 Loscalzo J, Kohane I, Barabasi AL. et al. Human disease classification in the postgenomic era: a complex systems approach to human pathobiology. Mol Syst Biol 2007; 3: 124
• 5 Hu G, Agarwal P. Human disease-drug network based on genomic expression profiles. PloS One 2009; 4: e6536
• 6 Stegmaier P, Krull M, Voss N. et al. Molecular mechanistic associations of human diseases. BMC Syst Biol 2010; 4: 1-9
• 7 Vidal M, Cusick ME, Barabási AL. et al. Interactome networks and human disease. Cell 2011; 144: 986-998
• 8 Hidalgo CA, Blumm N, Barabási AL. et al. A dynamic network approach for the study of human phenotypes. PLoS Comput Biol 2009; 5: e1000353
• 9 Li GW, Xie XS. Central dogma at the single-molecule level in living cells. Nature 2011; 475: 308-315
• 10 Fenimore PW, Frauenfelder H, McMahon BH. et al. Slaving: solvent fluctuations dominate protein dynamics and functions. Proc Natl Acad Sci 2002; 99: 16047-16051
• 11 Fitzpatrick AW, Debelouchina GT, Bayro MJ. et al. Atomic structure and hierarchical assembly of a cross-β amyloid fibril. Proc Natl Acad Sci 2013; 110: 5468-5473
• 12 Jimenez JL, Guijarro JI, Orlova E. et al. Cryo-electron microscopy structure of an SH3 amyloid fibril and model of the molecular packing. EMBO J 1999; 18: 815-821
• 13 Hussain R, Zubair H, Pursell S. et al. Neurodegenerative diseases: regenerative mechanisms and novel therapeutic approaches. Brain Sci 2018; 8: 177
• 14 Singh A, Ansari VA, Mahmood T. et al. Dendrimers: a neuroprotective lead in Alzheimer Disease: a review on its synthetic approach and applications. Drug Res 2022; 72: 417-423
• 15 Singh A, Ansari VA, Mahmood T. et al. Neurodegeneration: Microglia: Nf-Kappab Signaling Pathways. Drug Res 2022; 72: 496-499
• 16 Singh A, Maheshwari S. Dendrimers for neuro targeting. Int J Pharm Profession Res (IJPPR) 2023; 14: 124-130
• 17 Rezazadeh M, Khorrami A, Yeghaneh T. et al. Genetic factors affecting late-onset Alzheimer’s disease susceptibility. Neuromol Med 2016; 18: 37-49
• 18 Hornberger M, Piguet O. Episodic memory in frontotemporal dementia: a critical review. Brain 2012; 135: 678-692
• 19 Rizek P, Kumar N, Jog MS. et al. An update on the diagnosis and treatment of Parkinson disease. CMAJ 2016; 188: 1157-1165
• 20 Politi C, Ciccacci C, Novelli G. et al. Genetics and treatment response in Parkinson’s disease: an update on pharmacogenetic studies. Neuromol Med 2018; 20: 1-7
• 21 Schapira AH. Glucocerebrosidase and Parkinson disease: recent advances. Mol Cell Neurosci 2015; 66: 37-42
• 22 Marques O, Outeiro TF. Alpha-synuclein: from secretion to dysfunction and death. Cell Death Disease 2012; 3: e350
• 23 Niedzielska E, Smaga I, Gawlik M. et al. Oxidative stress in neurodegenerative diseases. Mol Neurobiol 2016; 53: 4094-4125
• 24 Erkkinen MG, Kim MO, Geschwind MD. et al. Clinical neurology and epidemiology of the major neurodegenerative diseases. Cold Spring Harbor Perspect Biol 2018; 10: a033118
• 25 Rai SN, Singh P. Advancement in the modelling and therapeutics of Parkinson’s disease. J Chem Neuroanat 2020; 104: 101752
• 26 Marsh SE, Blurton-Jones M. Neural stem cell therapy for neurodegenerative disorders: the role of neurotrophic support. Neurochem Int 2017; 106: 94-100
• 27 Thrash-Williams B, Karuppagounder SS, Bhattacharya D. et al. Methamphetamine-induced dopaminergic toxicity prevented owing to the neuroprotective effects of salicylic acid. Life Sci 2016; 154: 24-29
• 28 Northrop NA, Yamamoto BK. Methamphetamine effects on blood-brain barrier structure and function. Front Neurosci 2015; 9: 69
• 29 Pfrieger FW. Neurodegenerative diseases and cholesterol: seeing the field through the players. Front Aging Neurosci 2021; 13: 766587
• 30 Stephenson J, Nutma E, van der Valk P. et al. Inflammation in CNS neurodegenerative diseases. Immunology 2008; 154: 204-219
• 31 Marsh SE, Blurton-Jones M. Neural stem cell therapy for neurodegenerative disorders: the role of neurotrophic support. Neurochem Int 2017; 106: 94-100
• 32 Montero-Odasso M, Pieruccini-Faria F, Bartha R. et al. Motor phenotype in neurodegenerative disorders: gait and balance platform study design protocol for the Ontario neurodegenerative research initiative (ONDRI). J Alzheimer Dis 2017; 59: 707-721
• 33 Hussain R, Zubair H, Pursell S. et al. Neurodegenerative diseases: Regenerative mechanisms and novel therapeutic approaches. Brain Sci 2018; 8: 177
• 34 Guo JL, Lee VM. Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases. Nat Med 2014; 20: 130-138
• 35 Glenner GG, Wong CW. Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 1984; 120: 885-890
• 36 Orgeta V, Leung P, del-Pino-Casado R. et al. Psychological treatments for depression and anxiety in dementia and mild cognitive impairment. Cochrane Database Syst Rev 2022; 4: CD009125
• 37 Wimo A, Jönsson L, Bond J. et al. The worldwide economic impact of dementia 2010. Alzheimer Dement 2013; 9: 1
• 38 Goodman RA, Lochner KA, Thambisetty M. et al. Prevalence of dementia subtypes in United States medicare fee-for-service beneficiaries, 2011–2013. Alzheimer Dement 2017; 13: 28-37
• 39 Hanna K, Giebel C, Tetlow H. et al. Emotional and mental wellbeing following COVID-19 public health measures on people living with dementia and carers. J Geriatr Psychiatry Neurol 2022; 35: 344-352
• 40 Auluck PK, Chan HE, Trojanowski JQ. et al. Chaperone suppression of α-synuclein toxicity in a Drosophila model for Parkinson’s disease. Science 2002; 295: 865-868
• 41 Pfrieger FW. Neurodegenerative diseases and cholesterol: seeing the field through the players. Front Aging Neurosci 2021; 13: 766587
• 42 Stephenson J, Nutma E, van der Valk P. et al. Inflammation in CNS neurodegenerative diseases. Immunology 2018; 154: 204-219
• 43 Marsh SE, Blurton-Jones M. Neural stem cell therapy for neurodegenerative disorders: the role of neurotrophic support. Neurochem Int 2017; 106: 94-100
• 44 Varma H, Lo DC, Stockwell BR. et al. High throughput screening for neurodegeneration and complex disease phenotypes. Combinat Chem High Throughput Screen 2008; 11: 238-248
• 45 Przedborski S, Vila M, Jackson-Lewis V. et al. Series Introduction: Neurodegeneration: What is it and where are we?. J Clin Invest 2003; 111: 3-10
• 46 Woolley JD, Khan BK, Murthy NK. et al. The diagnostic challenge of psychiatric symptoms in neurodegenerative disease: rates of and risk factors for prior psychiatric diagnosis in patients with early neurodegenerative disease. J Clin Psychiatry 2011; 72: 4437
• 47 de Araújo FM, Cuenca-Bermejo L, Fernandez-Villalba E. et al. Role of microgliosis and NLRP3 inflammasome in Parkinson’s disease pathogenesis and therapy. Cell Mol Neurobiol 2022; 42: 1283-1300
• 48 Davis AA, Leyns CE, Holtzman DM. et al. Intercellular spread of protein aggregates in neurodegenerative disease. Ann Rev Cell Develop Biol 2018; 34: 545-568
• 49 Kosik KS, Joachim CL, Selkoe DJ. et al. Microtubule-associated protein tau (?) is a major antigenic component of paired helical filaments in Alzheimer disease. Alzheimer Dis Assoc Disord 1987; 1: 203
• 50 Kosik KS, Joachim CL, Selkoe DJ. Microtubule-associated protein tau (?) is a major antigenic component of paired helical filaments in Alzheimer disease. Alzheimer Dis Assoc Disord 1987; 1: 203
• 51 Qiu C, Kivipelto M, Von Strauss E. Epidemiology of Alzheimer’s disease: occurrence, determinants, and strategies toward intervention. Dialog Clin Neurosci 2009; 11: 111-128
• 52 Smith CJ, Anderton BH, Davis DR. et al. Tau isoform expression and phosphorylation state during differentiation of cultured neuronal cells. FEBS Lett 1995; 375: 243-248
• 53 Chami L, Checler F. BACE1 is at the crossroad of a toxic vicious cycle involving cellular stress and β-amyloid production in Alzheimer’s disease. Mol Neurodegener 2012; 7: 1-5
• 54 Tarpey P, Parnau J, Blow M. et al. Mutations in the DLG3 gene cause nonsyndromic X-linked mental retardation. Am J Hum Genet 2004; 75: 318-324
• 55 Hol EM, Roelofs RF, Moraal E. et al. Neuronal expression of GFAP in patients with Alzheimer pathology and identification of novel GFAP splice forms. Mol Psychiatry 2003; 8: 786-796
• 56 Andersen K, Launer LJ, Dewey ME. et al. Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies. Neurology 1999; 53: 1992-1997
• 57 Zhu H, Ding Q. Lower expression level of two RAGE alternative splicing isoforms in Alzheimer’s disease. Neurosci Lett 2015; 597: 66-70
• 58 Fu RH, Liu SP, Huang SJ. et al. Aberrant alternative splicing events in Parkinson’s disease. Cell Transplant 2013; 22: 653-661
• 59 Hoyer W, Cherny D, Subramaniam V. et al. Impact of the acidic C-terminal region comprising amino acids 109 −140 on α-synuclein aggregation in vitro. Biochemistry 2004; 43: 16233-16242
• 60 Brody KM, Taylor JM, Wilson GR. et al. Regional and cellular localisation of Parkin co-regulated gene in developing and adult mouse brain. Brain Res 2008; 1201: 177-186
• 61 Wilson GR, Wang HX, Egan GF. et al. Deletion of the Parkin co-regulated gene causes defects in ependymal ciliary motility and hydrocephalus in the quaking viable mutant mouse. Hum Mol Genet 2010; 19: 1593-1602
• 62 Gwozdzinska P. Hypercapnia impairs ENaC cell surface expression and function by promoting phosphorylation and polyubiquitination of ENaC beta-subunit in alveolar epithelial cells. Ph.D. Thesis, University of Giessen. 2018 http://geb.uni-giessen.de/geb/volltexte/2018/13668/
• 63 Gazit E. The “correctly folded” state of proteins: is it a metastable state?. Angew Chem Int Ed 2002; 41: 257-259
• 64 Perczel A, Hudáky P, Pálfi VK. et al. Dead-end street of protein folding: thermodynamic rationale of amyloid fibril formation. J Am Chem Soc 2007; 129: 14959-14965
• 65 Xue WF, Homans SW, Radford SE. et al. Systematic analysis of nucleation-dependent polymerization reveals new insights into the mechanism of amyloid self-assembly. Proc Natl Acad Sci 2008; 105: 8926-8931
• 66 Knowles TP, Waudby CA, Devlin GL. et al. An analytical solution to the kinetics of breakable filament assembly. Science 2009; 326: 1533-1537
• 67 Buell AK, Dhulesia A, White DA. et al. Detailed analysis of the energy barriers for amyloid fibril growth. Angew Chem Int Ed 2012; 51: 5247-5251
• 68 Jarrett JT, Lansbury PT. Amyloid fibril formation requires a chemically discriminating nucleation event: studies of an amyloidogenic sequence from the bacterial protein OsmB. Biochemistry 1992; 31: 12345-12352
• 69 Törnquist M, Michaels TC, Sanagavarapu K. et al. Secondary nucleation in amyloid formation. Chem Commun 2018; 54: 8667-8684
• 70 Linse S. Monomer-dependent secondary nucleation in amyloid formation. Biophys Rev 2017; 9: 329-338
• 71 Li D, Kaner RB. How nucleation affects the aggregation of nanoparticles. J Mater Chem 2007; 17: 2279-2282
• 72 Librizzi F, Rischel C. The kinetic behavior of insulin fibrillation is determined by heterogeneous nucleation pathways. Protein Sci 2005; 14: 3129-3134
• 73 Camino JD, Gracia P, Chen SW. et al. The extent of protein hydration dictates the preference for heterogeneous or homogeneous nucleation generating either parallel or antiparallel β-sheet α-synuclein aggregates. Chem Sci 2020; 11: 11902-11914
• 74 Wang C, Shah N, Thakur G. et al. α-Synuclein in α-helical conformation at air-water interface: implication of conformation and orientation changes during its accumulation/aggregation. Chem Commun 2010; 46: 6702-6704
• 75 Kakio A, Nishimoto SI, Yanagisawa K. et al. Interactions of amyloid β-protein with various gangliosides in raft-like membranes: importance of GM1 ganglioside-bound form as an endogenous seed for Alzheimer amyloid. Biochemistry 2002; 41: 7385-7390
• 76 Flach TL, Ng G, Hari A. et al. Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity. Nat Med 2011; 17: 479-487
• 77 Dorsey MP, Nguelifack BM, Yates EA. et al. Colorimetric detection of mutant β-Amyloid (1–40) membrane-active aggregation with biosensing vesicles. ACS Appl Bio Mater 2019; 2: 4966-4977
• 78 Pronchik J, He X, Giurleo JT. et al. In vitro formation of amyloid from α-synuclein is dominated by reactions at hydrophobic interfaces. J Am Chem Soc 2010; 132: 9797-9803
• 79 Necula M, Chirita CN, Kuret J. et al. Rapid anionic micelle-mediated α-synuclein fibrillization in vitro. J Biol Chem 2003; 278: 46674-46680
• 80 Galvagnion C, Brown JW, Ouberai MM. et al. Chemical properties of lipids strongly affect the kinetics of the membrane-induced aggregation of α-synuclein. Proc Natl Acad Sci 2016; 113: 7065-7070
• 81 Ambadipudi S, Biernat J, Riedel D. et al. Liquid-liquid phase separation of the microtubule-binding repeats of the Alzheimer-related protein Tau. Nat Commun 2017; 8: 275
• 82 Babinchak WM, Haider R, Dumm BK. et al. The role of liquid-liquid phase separation in aggregation of the TDP-43 low-complexity domain. J Biol Chem 2019; 294: 6306-6317
• 83 Beckmann ND. Multiscale Approaches to Complex Human Diseases. Doctoral Dissertation, Icahn School of Medicine at Mount Sinai.
• 84 Alberti S, Dormann D. Liquid–liquid phase separation in disease. Ann Rev Genet 2019; 53: 171-194
• 85 Grossberg GT, Manes F, Allegri RF. et al. The safety, tolerability, and efficacy of once-daily memantine (28 mg): a multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer’s disease taking cholinesterase inhibitors. CNS Drugs 2013; 27: 469-478
• 86 Littlejohns TJ, Henley WE, Lang IA. et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology 2014; 83: 920-928
• 87 Gupta PP, Pandey RD, Jha D. et al. Role of traditional nonsteroidal anti-inflammatory drugs in Alzheimer’s disease: a meta-analysis of randomized clinical trials. Am J Alzheimer Dis Dement 2015; 30: 178-182
• 88 Lee LK, Shahar S, Chin AV. et al. Docosahexaenoic acid-concentrated fish oil supplementation in subjects with mild cognitive impairment (MCI): a 12-month randomised, double-blind, placebo-controlled trial. Psychopharmacology 2013; 225: 605-612
• 89 Bo Y, Zhang X, Wang Y. et al. The n-3 polyunsaturated fatty acids supplementation improved the cognitive function in the Chinese elderly with mild cognitive impairment: a double-blind randomized controlled trial. Nutrients 2017; 9: 54
• 90 Gorelick PB, Furie KL, Iadecola C. et al. Defining optimal brain health in adults: a presidential advisory from the American Heart Association/American Stroke Association. Stroke 2017; 48: e284-e303
• 91 Bateman RJ, Xiong C, Benzinger TL. et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 2012; 367: 795-804
• 92 Pooler AM, Polydoro M, Wegmann S. et al. Propagation of tau pathology in Alzheimer’s disease: identification of novel therapeutic targets. Alzheimer Res Therap 2013; 5: 1-8
• 93 Salloway S, Sperling R, Fox NC. et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Eng J Med 2014; 370: 322-333
• 94 Kitwood T. The experience of dementia. Aging Mental Health 1997; 1: 13-22
• 95 Pohjasvaara T, Erkinjuntti T, Ylikoski R. et al. Clinical determinants of poststroke dementia. Stroke 1998; 29: 75-81
• 96 Greenamyre JT. The role of glutamate in neurotransmission and in neurologic disease. Arch Neurol 1986; 43: 1058-1063
• 97 Huang LK, Chao SP, Hu CJ. Clinical trials of new drugs for Alzheimer disease. J Biomed Sci 2020; 27: 1-3
• 98 Honig LS, Vellas B, Woodward M. et al. Trial of solanezumab for mild dementia due to Alzheimer’s disease. N Eng J Med 2018; 378: 321-330
• 99 Vassar R. BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease. Alzheimer Res Therapy 2014; 6: 1-4
• 100 Kennedy ME, Stamford AW, Chen X. et al. The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer’s disease patients. Sci Transl Med 2016; 8: 363ra150
• 101 Perry D, Sperling R, Katz R. et al. Building a roadmap for developing combination therapies for Alzheimer’s disease. Expert Rev Neurotherap 2015; 15: 327-333
• 102 Pedersen JT, Sigurdsson EM. Tau immunotherapy for Alzheimer’s disease. Trends Mol Med 2015; 21: 394-402
• 103 Panza F, Solfrizzi V, Seripa D. et al. Tau-based therapeutics for Alzheimer’s disease: active and passive immunotherapy. Immunotherapy 2016; 8: 1119-1134
• 104 Novak P, Schmidt R, Kontsekova E. et al. Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer’s disease: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Neurol 2017; 16: 123-134
• 105 Butterworth RF, Héroux M. Effect of pyrithiamine treatment and subsequent thiamine rehabilitation on regional cerebral amino acids and thiamine-dependent enzymes. J Neurochem 1989; 52: 1079-1084
• 106 Do Carmo S, Cuello AC. Modeling Alzheimer’s disease in transgenic rats. Mol Neurodegener 2013; 8: 1
• 107 Carter J, Thrasher S, Thornicroft G. Cognitive impairment and clozapine. Br J Psychiatry 1994; 164: 132-133
• 108 Chandler MJ, DeLeo J, Carney JM. An unanesthetized-gerbil model of cerebral ischemia-induced behavioral changes. J Pharmacol Meth 1985; 14: 137-146
• 109 Lu YQ, Luo Y, He ZF. et al. Hydroxysafflor yellow A ameliorates homocysteine-induced Alzheimer-like pathologic dysfunction and memory/synaptic disorder. Rejuv Res 2013; 16: 446-452
• 110 Chui DH, Tanahashi H, Ozawa K. et al. Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation. Nat Med 1999; 5: 560-564
• 111 Citron M, Westaway D, Xia W. et al. Mutant presenilins of Alzheimer’s disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice. Nat Med 1997; 3: 67-72
• 112 Clandinin MT, Cheema S, Field CJ. et al. Dietary lipids influence insulin action. Ann New York Acad Sci 1993; 683: 151-163
• 113 Collier TJ, Gash DM, Sladek JR. Transplantation of norepinephrine neurons into aged rats improves performance of a learned task. Brain research 1988; 448: 77-87
• 114 de Souza Silva MA, Lenz B, Rotter A. et al. Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism. Proc Natl Acad Sci 2013; 110: 15097-15102
• 115 Desrumaux C, Pisoni A, Meunier J. et al. Increased amyloid-β peptide-induced memory deficits in phospholipid transfer protein (PLTP) gene knockout mice. Neuropsychopharmacology 2013; 38: 817-825
• 116 Dhingra D, Parle M, Kulkarni SK. et al. Effect of combination of insulin with dextrose, D (-) fructose and diet on learning and memory in mice. Indian J Pharmacol 2003; 35: 151-156
• 117 Bilkei-Gorzo A. Genetic mouse models of brain ageing and Alzheimer’s disease. Pharmacol Therap 2014; 142: 244-257
• 118 Bhattacharya SK, Kumar A, Jaiswal AK. et al. Effect of Mentat®, a herbal formulation, on experimental models of Alzheimer’s disease and central cholinergic markers in rats. Fitoterapia (Milano) 1995; 66: 216-222
• 119 Bales KR, Liu F, Wu S. et al. Human APOE isoform-dependent effects on brain β-amyloid levels in PDAPP transgenic mice. J Neurosci 2009; 29: 6771-6779
• 120 Fisher A, Hanin I. Potential animal models for senile dementia of Alzheimer’s type, with emphasis on AF64A-induced cholinotoxicity. Ann Rev Pharmacol Toxicol 1986; 26: 161-181
• 121 Flood JF, Morley JE. Learning and memory in the SAMP8 mouse. Neurosci Biobehav Rev 1997; 22: 1-20
• 122 Ganguly R, Guha D. Alteration of brain monoamines & EEG wave pattern in rat model of Alzheimer’s disease & protection by Moringa oleifera. Indian J Med Res 2008; 128: 744-751
• 123 Ghribi O, Golovko MY, Larsen B. et al. Deposition of iron and β-amyloid plaques is associated with cortical cellular damage in rabbits fed with long-term cholesterol-enriched diets. J Neurochem 2006; 99: 438-449
• 124 Gong CX, Liu F, Grundke-Iqbal I. et al. Dysregulation of protein phosphorylation/dephosphorylation in Alzheimer’s disease: a therapeutic target. J Biomed Biotechnol 2006; 31825
• 125 Hu ZY, Liu G, Cheng XR. et al. an active fraction extracted from Danggui–Shaoyao–San, decreases β-amyloid content and deposition, improves LTP reduction and prevents spatial cognition impairment in SAMP8 mice. Exp Gerontol 2012; 47: 14-22