Open Access Open Access  Restricted Access Subscription or Fee Access

The Pathophysiology, Diagnosis and Some Management Approaches of Alzheimer’s Disease: An Overview

Asad Jamal Ansari, Mohammad Monawwar, Nishat Fatima


Alzheimer’s disease is the greatest mutual cause of dementia globally, with the occurrence ongoing to grow in part because of the aging world populace. This neurodegenerative disease process is categorized characteristically by 2 mark pathologies: β-amyloid plaque deposition and neurofibrillary masses of hyperphosphorylated tau. Diagnosis is grounded on biomarkers restrained in vivo even beforehand the onset of clinical dementia symptoms. No solitary biomarker can by itself properly diagnose AD. A grouping of biomarkers measured over imaging and cerebrospinal fluid produces well diagnostic precision. However amyloid PET imaging and CSF heights of amyloid and tau deposits are progressively used in AD clinical trials to increase diagnostic declaration in enrolled subjects,monotonous use of these biomarkers in clinical locations is still early because of the risk of overdiagnosis, increased cost and/or invasiveness of the valuation method. Treatment is currently targeted toward symptomatic therapy, in which some of the treatment approaches are mentioned in this review, though the more research and trials are underway who’s objective is to deduce the production and overall burden of pathology within the brain. Now, we deliberate recent developments in our understanding of the clinical assessment and treatment of Alzheimer’s disease, with updates concerning clinical trials still in progress.


Alzheimer’s disease, Biomarkers, Acetylcholinesterase (AChE) inhibitors, Amyloid cascade hypothesis, and Dementia

Full Text:



Wu Y, Li Z, Huang YY, Wu D, Luo HB. Novel Phosphodiesterase Inhibitors for Cognitive Improvement in Alzheimer’s Disease: Miniperspective. Journal of Medicinal Chemistry. 2018 Jan 24;61(13):5467-83.

Kamil K, Yazid MD, Idrus RB, Das S, Kumar J. Peripheral Demyelinating Diseases: From Biology to Translational Medicine. Frontiers in neurology. 2019 Mar 19;10:87.

Newman M, Kretzschmar D, Khan I, Chen M, Verdile G, Lardelli M. Animal models of Alzheimer’s disease. InAnimal models for the study of human disease 2017 Jan 1 (pp. 1031-1085). Academic Press.

Canter RG, Penney J, Tsai LH. The road to restoring neural circuits for the treatment of Alzheimer's disease. Nature. 2016 Nov;539(7628):187-96.

Parker K, Rhee Y. Alzheimer’s Disease Warning Signs: Gender and Education Influence Modifiable Risk Factors—A Pilot Survey Study. Journal of the American College of Nutrition. 2020 Sep 2:1-6.

Mar J, Soto-Gordoa M, Arrospide A, Moreno-Izco F, Martínez-Lage P. Fitting the epidemiology and neuropathology of the early stages of Alzheimer’s disease to prevent dementia. Alzheimer's research & therapy. 2015 Dec 1;7(1):2.

Kingston A, Comas-Herrera A, Jagger C. Forecasting the care needs of the older population in England over the next 20 years: estimates from the Population Ageing and Care Simulation (PACSim) modelling study. The Lancet Public Health. 2018 Sep 1;3(9):e447-55.

Philip S, Kaj B, Breteler Monique MB, de Strooper Bart FG, Stephen S. Van der Flier Wiesje Maria. Alzheimer's disease. The Lancet. 2016;388(10043):505-17.

Cummings J, Lee G, Ritter A, Sabbagh M, Zhong K. Alzheimer's disease drug development pipeline: 2019. Alzheimer's & Dementia: Translational Research & Clinical Interventions. 2019 Jan 1;5:272-93.

Jack Jr CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E. Contributors, 2018. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement.;14(4):535-62.

Lee JC, Kim SJ, Hong S, Kim Y. Diagnosis of Alzheimer’s disease utilizing amyloid and tau as fluid biomarkers. Experimental & molecular medicine. 2019 May 9;51(5):1-0.

Frisoni GB, Boccardi M, Barkhof F, Blennow K, Cappa S, Chiotis K, Démonet JF, Garibotto V, Giannakopoulos P, Gietl A, Hansson O. Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers. The Lancet Neurology. 2017 Aug 1;16(8):661-76.

Jack Jr CR, Albert M, Knopman DS, McKhann GM, Sperling RA, Carillo M, Thies W, Phelps CH. Introduction to revised criteria for the diagnosis of Alzheimer’s disease: National Institute on Aging and the Alzheimer Association Workgroups. Alzheimer's & dementia: the journal of the Alzheimer's Association. 2011 May;7(3):257-62.

Petersen RC, Parisi JE, Dickson DW, Johnson KA, Knopman DS, Boeve BF, Jicha GA, Ivnik RJ, Smith GE, Tangalos EG, Braak H. Neuropathologic features of amnestic mild cognitive impairment. Archives of neurology. 2006 May 1;63(5):665-72.

Feldman HH, Lane R. on behalf of the Study 304 Group. Rivastigmine: a placebo controlled trial of twice daily and three times daily regimens in patients with Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2007;78:1056-63.

Winblad B, Machado JC. Use of rivastigmine transdermal patch in the treatment of Alzheimer's disease. Expert opinion on drug delivery. 2008 Dec 1;5(12):1377-86.

Yiannopoulou KG, Papageorgiou SG. Current and future treatments for Alzheimer’s disease. Therapeutic advances in neurological disorders. 2013 Jan;6(1):19-33.

Hampel H, Mesulam MM, Cuello AC, Farlow MR, Giacobini E, Grossberg GT, Khachaturian AS, Vergallo A, Cavedo E, Snyder PJ, Khachaturian ZS. The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain. 2018 Jul 1;141(7):1917-33.

Hampel H, Mesulam MM, Cuello AC, Farlow MR, Giacobini E, Grossberg GT, Khachaturian AS, Vergallo A, Cavedo E, Snyder PJ, Khachaturian ZS. The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain. 2018 Jul 1;141(7):1917-33.

Kumar A, Singh A. A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacological reports. 2015 Apr 1;67(2):195-203.

Mishra S, Palanivelu K. The effect of curcumin (turmeric) on Alzheimer's disease: An overview. Annals of Indian Academy of Neurology. 2008 Jan;11(1):13–19.

Weekley CM, He C. Developing drugs targeting transition metal homeostasis. Current opinion in chemical biology. 2017 Apr 1;37:26-32.

Prakash A, Dhaliwal GK, Kumar P, Majeed AB. Brain biometals and Alzheimer's disease–boon or bane?. International Journal of Neuroscience. 2017 Feb 1;127(2):99-108.

Liu Z, Zhang A, Sun H, Han Y, Kong L, Wang X. Two decades of new drug discovery and development for Alzheimer's disease. RSC advances. 2017;7(10):6046-58.

Mohamed T, Shakeri A, Rao PP. Amyloid cascade in Alzheimer's disease: recent advances in medicinal chemistry. European journal of medicinal chemistry. 2016 May 4;113:258-72.

Sultzer DL, Marder SR. Older Brains are Different: Brain–Behavior Studies and Their Clinical Utility. The American Journal of Geriatric Psychiatry. 2017 Jan 1;25(1):11-2.Chase TN, Farlow MR, Clarence–Smith K. Donepezil Plus Solifenacin (CPC–201) Treatment for Alzheimer’s Disease. Neurotherapeutics. 2017;14(2):405–416.

UCSF Weill Institute for Neurosciences: Memory and Aging Center. What is dementia?, Accessed June 11, 2020.

Alzheimer's Association. 2015 Alzheimer's disease facts and figures. Alzheimer's & Dementia. 2015 Mar;11(3):332-84.

Alzheimer’s Association International Conference 2018. Press release. First practice guidelines for clinical evaluation of Alzheimer’s disease and other dementias for primary and specialty care., July 22, 2018. Accessed May 6, 2020.

Wessels AM, Tariot PN, Zimmer JA, Selzler KJ, Bragg SM, Andersen SW, Landry J, Krull JH, Downing AM, Willis BA, Shcherbinin S. Efficacy and safety of lanabecestat for treatment of early and mild Alzheimer disease: the AMARANTH and DAYBREAK-ALZ randomized clinical trials. JAMA neurology. 2020 Feb 1;77(2):199-209.

Cordell CB, Borson S, Boustani M, Chodosh J, Reuben D, Verghese J, Thies W, Fried LB, Medicare Detection of Cognitive Impairment Workgroup. Alzheimer's Association recommendations for operationalizing the detection of cognitive impairment during the Medicare Annual Wellness Visit in a primary care setting. Alzheimer's & Dementia. 2013 Mar 1;9(2):141-50.

Breitner JC. Mild cognitive impairment and progression to dementiaAbout mild cognitive impairment: New findings. Neurology. 2014 Jan 28;82(4):e34-5.


Rasmussen J, Langerman H. Alzheimer’s disease–why we need early diagnosis. Degenerative Neurological and Neuromuscular Disease. 2019;9:123.

Dubois B, Padovani A, Scheltens P, Rossi A, Dell’Agnello G. Timely diagnosis for Alzheimer’s disease: a literature review on benefits and challenges. Journal of Alzheimer's disease. 2016 Jan 1;49(3):617-31.

Deb A, Thornton JD, Sambamoorthi U, Innes K. Direct and indirect cost of managing Alzheimer’s disease and related dementias in the United States. Expert review of pharmacoeconomics & outcomes research. 2017 Mar 4;17(2):189-202.

Weimer DL, Sager MA. Early identification and treatment of Alzheimer's disease: social and fiscal outcomes. Alzheimer's & Dementia. 2009 May 1;5(3):215-26.

de Vugt ME, Verhey FR. The impact of early dementia diagnosis and intervention on informal caregivers. Progress in neurobiology. 2013 Nov 1;110:54-62.

McKhann GM, Albert MS, Sperling RA. Changing diagnostic concepts of Alzheimer’s Disease. InAlzheimer's disease-modernizing concept, biological diagnosis and therapy 2012 (Vol. 28, pp. 115-121). Karger Publishers.

Bloudek LM, Spackman DE, Blankenburg M, Sullivan SD. Review and meta-analysis of biomarkers and diagnostic imaging in Alzheimer's disease. Journal of Alzheimer's Disease. 2011 Jan 1;26(4):627-45.

Vickrey BG, Mittman BS, Connor KI, Pearson ML, Della Penna RD, Ganiats TG, DeMonte Jr RW, Chodosh J, Cui X, Vassar S, Duan N. The effect of a disease management intervention on quality and outcomes of dementia care: a randomized, controlled trial. Annals of internal medicine. 2006 Nov 21;145(10):713-26.

Voisin T, Vellas B. Diagnosis and treatment of patients with severe Alzheimer’s disease. Drugs & aging. 2009 Feb 1;26(2):135-44.

Grossberg GT, Christensen DD, Griffith PA, Kerwin DR, Hunt G, Hall EJ. The art of sharing the diagnosis and management of Alzheimer's disease with patients and caregivers: recommendations of an expert consensus panel. Primary care companion to the Journal of clinical psychiatry. 2010;12(1).

Braak H, Braak EV. Staging of Alzheimer's disease-related neurofibrillary changes. Neurobiology of aging. 1995 May 1;16(3):271-8.

Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science. 1992 Apr 10;256(5054):184-6.

Panza F, Lozupone M, Logroscino G, Imbimbo BP. A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease. Nature Reviews Neurology. 2019 Feb;15(2):73-88.

Roses AD. Apolipoprotein E affects the rate of Alzheimer disease expression: β-amyloid burden is a secondary consequence dependent on APOE genotype and duration of disease. Journal of Neuropathology & Experimental Neurology. 1994 Sep 1;53(5):429-37.

Henry W, Querfurth HW, LaFerla FM. Mechanisms of disease Alzheimer’s disease. New Engl J Med. 2010;362:329-44.

Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris JC, Yarasheski KE, Bateman RJ. Decreased clearance of CNS β-amyloid in Alzheimer’s disease. Science. 2010 Dec 24;330(6012):1774-.

Knopman DS, Jack Jr CR, Wiste HJ, Weigand SD, Vemuri P, Lowe VJ, Kantarci K, Gunter JL, Senjem ML, Mielke MM, Roberts RO. Brain injury biomarkers are not dependent on β‐amyloid in normal elderly. Annals of neurology. 2013 Apr;73(4):472-80.

Drachman DA. The amyloid hypothesis, time to move on: Amyloid is the downstream result, not cause, of Alzheimer's disease. Alzheimer's & Dementia. 2014 May 1;10(3):372-80.

Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Ferris S, Reichert M. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. New England Journal of Medicine. 2014 Jan 23;370(4):322-33.

Monsell SE, Kukull WA, Roher AE, Maarouf CL, Serrano G, Beach TG, Caselli RJ, Montine TJ, Reiman EM. Characterizing apolipoprotein E ε4 carriers and noncarriers with the clinical diagnosis of mild to moderate Alzheimer dementia and minimal β-amyloid peptide plaques. JAMA neurology. 2015 Oct 1;72(10):1124-31.

Jack Jr CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB. NIA-AA research framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018; 14: 535–62.

Perry EK, Gibson PH, Blessed G, Perry RH, Tomlinson BE. Neurotransmitter enzyme abnormalities in senile dementia: Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue. Journal of the neurological sciences. 1977 Nov 1;34(2):247-65.

Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, Ballard C, Banerjee S, Burns A, Cohen-Mansfield J, Cooper C. Dementia prevention, intervention, and care. The Lancet. 2017 Dec 16;390(10113):2673-734.

Adler G, Mueller B, Articus K. The transdermal formulation of rivastigmine improves caregiver burden and treatment adherence of patients with Alzheimer's disease under daily practice conditions. International journal of clinical practice. 2014 Apr;68(4):465-70.

Petersen RC, Parisi JE, Dickson DW, Johnson KA, Knopman DS, Boeve BF, Jicha GA, Ivnik RJ, Smith GE, Tangalos EG, Braak H. Neuropathologic features of amnestic mild cognitive impairment. Archives of neurology. 2006 May 1;63(5):665-72.

Braak H, Del Tredici K. Evolutional aspects of Alzheimer's disease pathogenesis. Journal of Alzheimer's Disease. 2013 Jan 1;33(s1):S155-61.

Ryan NS, Keihaninejad S, Shakespeare TJ, Lehmann M, Crutch SJ, Malone IB, Thornton JS, Mancini L, Hyare H, Yousry T, Ridgway GR. Magnetic resonance imaging evidence for presymptomatic change in thalamus and caudate in familial Alzheimer’s disease. Brain. 2013 May 1;136(5):1399-414.

Sheline YI, Morris JC, Snyder AZ, Price JL, Yan Z, D'Angelo G, Liu C, Dixit S, Benzinger T, Fagan A, Goate A. APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Aβ42. Journal of Neuroscience. 2010 Dec 15;30(50):17035-40.

Wirth M, Madison CM, Rabinovici GD, Oh H, Landau SM, Jagust WJ. Alzheimer's disease neurodegenerative biomarkers are associated with decreased cognitive function but not β-amyloid in cognitively normal older individuals. Journal of Neuroscience. 2013 Mar 27;33(13):5553-63.

Jack Jr CR, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. The Lancet Neurology. 2010 Jan 1;9(1):119-28.

Edmonds EC, Delano-Wood L, Galasko DR, Salmon DP, Bondi MW. Subtle cognitive decline and biomarker staging in preclinical Alzheimer’s disease. Journal of Alzheimer's disease. 2015 Jan 1;47(1):231-42.

Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. Journal of Neuropathology & Experimental Neurology. 2011 Nov 1;70(11):960-9.

Bondi MW, Edmonds EC, Salmon DP. Alzheimer’s disease: past, present, and future. Journal of the International Neuropsychological Society: JINS. 2017 Oct;23(9-10):818-31.

Ossenkoppele R, Smith R, Ohlsson T, Strandberg O, Mattsson N, Insel PS, Palmqvist S, Hansson O. Associations between tau, Aβ, and cortical thickness with cognition in Alzheimer disease. Neurology. 2019 Feb 5;92(6):e601-12.

Chen G, Rajkowska G, Du F, Seraji‐Bozorgzad N, Manji HK. Enhancement of hippocampal neurogenesis by lithium. Journal of neurochemistry. 2000 Oct;75(4):1729-34.

Forlenza OV, De-Paula VD, Diniz BS. Neuroprotective effects of lithium: implications for the treatment of Alzheimer’s disease and related neurodegenerative disorders. ACS chemical neuroscience. 2014 Jun 18;5(6):443-50.

Dell’Osso L, Del Grande C, Gesi C, Carmassi C, Musetti L. A new look at an old drug: neuroprotective effects and therapeutic potentials of lithium salts. Neuropsychiatric disease and treatment. 2016;12:1687-703.

Phiel CJ, Wilson CA, Lee VM, Klein PS. GSK-3α regulates production of Alzheimer's disease amyloid-β peptides. Nature. 2003 May;423(6938):435-9.

Canter RG, Penney J, Tsai LH. The road to restoring neural circuits for the treatment of Alzheimer's disease. Nature. 2016 Nov;539(7628):187-96.

Buzsáki G, Wang XJ. Mechanisms of gamma oscillations. Annual review of neuroscience. 2012 Jul 21;35:203-25.

Sederberg PB, Schulze-Bonhage A, Madsen JR, Bromfield EB, Litt B, Brandt A, Kahana MJ. Gamma oscillations distinguish true from false memories. Psychological science. 2007 Nov;18(11):927-32.

Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, Gillingham TZ, Mathys H, Seo J, Kritskiy O, Abdurrob F, Adaikkan C. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 2016 Dec;540(7632):230-5.

Mayeux R. Epidemiology of neurodegeneration. Annual review of neuroscience. 2003 Mar;26(1):81-104.

Castellano JM, Kim J, Stewart FR, Jiang H, DeMattos RB, Patterson BW, Fagan AM, Morris JC, Mawuenyega KG, Cruchaga C, Goate AM. Human apoE isoforms differentially regulate brain amyloid-β peptide clearance. Science translational medicine. 2011 Jun 29;3(89):89ra57-.

Cataldo AM, Peterhoff CM, Troncoso JC, Gomez-Isla T, Hyman BT, Nixon RA. Endocytic pathway abnormalities precede amyloid β deposition in sporadic Alzheimer’s disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. The American journal of pathology. 2000 Jul 1;157(1):277-86.

Li J, Kanekiyo T, Shinohara M, Zhang Y, LaDu MJ, Xu H, Bu G. Differential regulation of amyloid-β endocytic trafficking and lysosomal degradation by apolipoprotein E isoforms. Journal of Biological Chemistry. 2012 Dec 28;287(53):44593-601.

Holtzman DM, Herz J, Bu G. Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease. Cold Spring Harbor perspectives in medicine. 2012 Mar 1;2(3):a006312.

Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nature Reviews Neurology. 2013 Feb;9(2):106-18.

Kuszczyk MA, Sanchez S, Pankiewicz J, Kim J, Duszczyk M, Guridi M, Asuni AA, Sullivan PM, Holtzman DM, Sadowski MJ. Blocking the interaction between apolipoprotein E and Aβ reduces intraneuronal accumulation of Aβ and inhibits synaptic degeneration. The American journal of pathology. 2013 May 1;182(5):1750-68.

Liu Q, Wu WH, Fang CL, Li RW, Liu P, Lei P, Hu J, Sun X, Zheng YZ, Zhao YF, Li YM. Mapping ApoE/Aβ binding regions to guide inhibitor discovery. Molecular BioSystems. 2011;7(5):1693-700.

Sadowski MJ, Pankiewicz J, Scholtzova H, Mehta PD, Prelli F, Quartermain D, Wisniewski T. Blocking the apolipoprotein E/amyloid-β interaction as a potential therapeutic approach for Alzheimer's disease. Proceedings of the National Academy of Sciences. 2006 Dec 5;103(49):18787-92.

Yang J, Ji Y, Mehta P, Bates KA, Sun Y, Wisniewski T. Blocking the apolipoprotein E/amyloid-β interaction reduces fibrillar vascular amyloid deposition and cerebral microhemorrhages in TgSwDI mice. Journal of Alzheimer's Disease. 2011 Jan 1;24(2):269-85.

Cramer PE, Cirrito JR, Wesson DW, Lee CD, Karlo JC, Zinn AE, Casali BT, Restivo JL, Goebel WD, James MJ, Brunden KR. ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models. science. 2012 Mar 23;335(6075):1503-6.

Kim J, Castellano JM, Jiang H, Basak JM, Parsadanian M, Pham V, Mason SM, Paul SM, Holtzman DM. Overexpression of low-density lipoprotein receptor in the brain markedly inhibits amyloid deposition and increases extracellular Aβ clearance. Neuron. 2009 Dec 10;64(5):632-44.

Dodart JC, Marr RA, Koistinaho M, Gregersen BM, Malkani S, Verma IM, Paul SM. Gene delivery of human apolipoprotein E alters brain Aβ burden in a mouse model of Alzheimer's disease. Proceedings of the National Academy of Sciences. 2005 Jan 25;102(4):1211-6.

Hudry E, Dashkoff J, Roe AD, Takeda S, Koffie RM, Hashimoto T, Scheel M, Spires-Jones T, Arbel-Ornath M, Betensky R, Davidson BL. Gene transfer of human Apoe isoforms results in differential modulation of amyloid deposition and neurotoxicity in mouse brain. Science translational medicine. 2013 Nov 20;5(212):212ra161-.

Kim J, Eltorai AE, Jiang H, Liao F, Verghese PB, Kim J, Stewart FR, Basak JM, Holtzman DM. Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis. Journal of Experimental Medicine. 2012 Nov 19;209(12):2149-56.

Liao F, Hori Y, Hudry E, Bauer AQ, Jiang H, Mahan TE, Lefton KB, Zhang TJ, Dearborn JT, Kim J, Culver JP. Anti-ApoE antibody given after plaque onset decreases Aβ accumulation and improves brain function in a mouse model of Aβ amyloidosis. Journal of Neuroscience. 2014 May 21;34(21):7281-92.

Brodbeck J, McGuire J, Liu Z, Meyer-Franke A, Balestra ME, Jeong DE, Pleiss M, McComas C, Hess F, Witter D, Peterson S. Structure-dependent impairment of intracellular apolipoprotein E4 trafficking and its detrimental effects are rescued by small-molecule structure correctors. Journal of Biological Chemistry. 2011 May 13;286(19):17217-26.

Chen HK, Liu Z, Meyer-Franke A, Brodbeck J, Miranda RD, McGuire JG, Pleiss MA, Ji ZS, Balestra ME, Walker DW, Xu Q. Small molecule structure correctors abolish detrimental effects of apolipoprotein E4 in cultured neurons. Journal of Biological Chemistry. 2012 Feb 17;287(8):5253-66.

Wang C, Najm R, Xu Q, Jeong DE, Walker D, Balestra ME, Yoon SY, Yuan H, Li G, Miller ZA, Miller BL. Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector. Nature medicine. 2018 May;24(5):647-57.

Donkin JJ, Stukas S, Hirsch-Reinshagen V, Namjoshi D, Wilkinson A, May S, Chan J, Fan J, Collins J, Wellington CL. ATP-binding cassette transporter A1 mediates the beneficial effects of the liver X receptor agonist GW3965 on object recognition memory and amyloid burden in amyloid precursor protein/presenilin 1 mice. Journal of Biological Chemistry. 2010 Oct 29;285(44):34144-54.

Fitz NF, Cronican A, Pham T, Fogg A, Fauq AH, Chapman R, Lefterov I, Koldamova R. Liver X receptor agonist treatment ameliorates amyloid pathology and memory deficits caused by high-fat diet in APP23 mice. Journal of Neuroscience. 2010 May 19;30(20):6862-72.

Koldamova RP, Lefterov IM, Staufenbiel M, Wolfe D, Huang S, Glorioso JC, Walter M, Roth MG, Lazo JS. The liver X receptor ligand T0901317 decreases amyloid β production in vitro and in a mouse model of Alzheimer's disease. Journal of Biological Chemistry. 2005 Feb 11;280(6):4079-88.

Riddell DR, Zhou H, Comery TA, Kouranova E, Lo CF, Warwick HK, Ring RH, Kirksey Y, Aschmies S, Xu J, Kubek K. The LXR agonist TO901317 selectively lowers hippocampal Aβ42 and improves memory in the Tg2576 mouse model of Alzheimer's disease. Molecular and Cellular Neuroscience. 2007 Apr 1;34(4):621-8.

Laskowitz DT, Lei B, Dawson HN, Wang H, Bellows ST, Christensen DJ, Vitek MP, James ML. The apoE-mimetic peptide, COG1410, improves functional recovery in a murine model of intracerebral hemorrhage. Neurocritical care. 2012 Apr 1;16(2):316-26.

Laskowitz DT, McKenna SE, Song P, Wang H, Durham L, Yeung N, Christensen D, Vitek MP. COG1410, a novel apolipoprotein E–based peptide, improves functional recovery in a murine model of traumatic brain injury. Journal of neurotrauma. 2007 Jul 1;24(7):1093-107.


  • There are currently no refbacks.

Copyright (c) 2021 Research & Reviews: A Journal of Drug Design & Discovery