RECENT ADVANCES IN ALZHEIMER'S DISEASE: CAUSES AND TREATMENT

Authors

  • Kiranjit Kaur G. H. G. Khalsa College of Pharmacy, Gurusar Sadhar, Ludhiana (India) 141104
  • Rajneet Kaur Gurusar Sadhar
  • Manjinder Kaur Gurusar Sadhar

Keywords:

Alzheimer`s disease, Alzheimer causes and treatment

Abstract

Alzheimer's disease (AD) is a destructive neurodegenerative disorder characterized by progressive memory defeat and impairment in behavior, language, and visuospatial skills. Neuropsychiatric symptoms such as apathy, depression, aggression, agitation, sleep disruption, and psychosis are now recognized as core symptoms of AD that are expressed to varying degrees throughout the course of disease. The neuro pathological features of AD comprise extracellular senile plaques constituted of β-amyloid (Aβ) pledges, intracellular neurofibrillary tangles (NFTs), and cerebral atrophy; others include apolipoprotein E, oxidative stress, mitochondrial dysfunction and cholinergic hypothesis. Anti-amyloid therapy is available for the treatment of Alzheimer's disease, others are anticholinergic therapy, and therapy for mitochondrial dysfunction, γ-secretase inhibitors (GSI) and modulators (GSM), ð›½-secretase (BACE1) inhibitors, Glial modulating drugs includes RAGE receptor antagonists, TNF-α antagonists, neuroprotective drugs such as antioxidants, phosphodiesterase inhibitors, PPARγ agonists, and anti-tau or tau modulators like microtubule stabilizers, kinase inhibitors. This review includes discussion on neurobiological mechanisms and newly developed compounds which have lesser side effects and are proving more efficient for treatment of Alzheimer's disease.

 

Downloads

Download data is not yet available.

References

Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev 2001;81:741-66.

Querfurth HW, LaFerla FM. Alzheimer's disease. N Engl J Med 2010;362:329-44.

Mayeux R. Clinical practice. early Alzheimer's disease. N Engl J Med 2010;362:2194-201.

Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer's disease. Alzheimer’s Dementia 2007;3:186-91.

Findeis MA. The role of amyloid beta peptide-42 in Alzheimer's disease. Pharmacol Ther 2007;116:266-86.

Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002;297:353-6.

Pimplikar SW. Reassessing the amyloid cascade hypothesis of Alzheimer's disease. Int J Biochem Cell Biol 2009;41:1261-8.

Daviglus ML, Plassman BL, Pirzada A, Bell CC, Bowen PE, Burke JR, et al. Risk factors and preventive interventions for Alzheimer disease: state of the science. Arch Neurol 2011;68:1185-90.

Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol 2011;10:819–28.

Ersche KD, Barnes A, Jones PS, Morein-Zamir S, Robbins TW, Bullmore ET. Abnormal structure of front striatal brain systems is associated with aspects of impulsivity and compulsivity in cocaine dependence. Brain 2011;134:2013–24.

Etgen T, Sander D, Bickel H, Forstl H. Mild cognitive impairment and dementia: the importance of modifiable risk factors. Deutsches Ärzteblatt 2011;108:743–50.

Bateman RJ, Aisen PS, De Strooper B, Fox NC, Lemere CA. Autosomal-dominant Alzheimer’s disease: a review and proposal for the prevention of Alzheimer’s disease. Alzheimer's Res Ther 2011;3:1.

Blennow K, de Leon MJ, Zetterberg H. Alzheimer’s disease. Lancet 2006;368:387-403.

Qiu C, Kivipelto M, Agüero-Torres H, Winblad B, Fratiglioni L. Risk and protective effects of the APOE gene towards Alzheimer’s disease in the Kungsholmen project: variation by age and sex. J Neurol Neurosurg Psychiatry 2004;75:828-33.

Swan, Lee Y. Systematic review of behavioral health risks and cognitive health in older adults. Int Psychogeriatrics 2010;20:174.

Giunta B, Deng J, Jin J, Sadic E, Rum S, Zhou H, et al. Evaluation of how cigarette smoke is a direct risk factor for Alzheimer’s disease. Technol Innovation 2012;14:39–48.

Ding J, Eigenbrodt ML, Hutchinson RG, Folsom AR, Harris TB, Nieto FJ, et al. Alcohol intake and cerebral abnormalities on magnetic resonance imaging in a community-based population of middle-aged adults: the atherosclerosis risk in communities (ARIC) study. Stroke 2004;35:16-21.

Paul CA, Au R, Fredman L, Massaro JM, Seshadri S, Decarli C, et al. Association of alcohol consumption with brain volume in the framingham study. Arch Neurol 2008;65:1363-7.

Cognitive Function and Decline in Obesity in Press; 2012.

Povova J, Pastucha D, Sery O, Matejkova M, andJanout V. Is cardiovascular disease a risk factor for Alzheimer’s disease? Exp Clin Cardiol 2014;20:1-6.

Qiu C, Winblad B, Fratiglioni L. The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol 2005;4:487-99.

Yasar S, Corrada M, Broo kmeyer R, Kawas C. Calcium-channel blockers and risk of AD: the baltimore longitudinal study of aging. Neurobiol Aging 2005;26:157-63.

Khachaturian AS, Zandi PP, Lyketsos CG, Hayden KM, Skoog I, Norton MC, et al. Antihypertensive medication use and incident Alzheimer disease: the cache county study. Arch Neurol 2006;63:686-92.

Beishon LC, Harrison JK, Harwood RH, Robinson TG, Gladman JR, Conroy SP. The evidence for treating hypertension in older people with dementia: a systematic review. J Hum Hypertens 2014;28:283-7.

Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol 2004;61:661-6.

Akomolafe A, Beiser A, Meigs JB, Au R, Green RC, Farrer LA, et al. Diabetes mellitus and risk of developing Alzheimer disease: results from the framingham study. Arch Neurol 2006;63:1551-5.

Irie F, Fitzpatrick AL, Lopez OL, Kuller LH, Peila R, Newman AB, et al. Enhanced risk for Alzheimer disease in persons with type 2 diabetes and APOE e4: the cardiovascular health study cognition study. Arch Neurol 2008;65:89-93.

Freude S, Schilbach K, Schubert M. The role of IGF-1 receptor and insulin receptor signaling for the pathogenesis of Alzheimer's disease: from model organisms to human disease. Curr Alzheimer Res 2009;6:213–23.

Plum L, Schubert M, Bruning JC. The role of insulin receptor signaling in the brain. Trends Endocrinol Metab 2005;16:59–65.

Horwood JM, Dufour F, Laroche S, Davis S. Signaling mechanisms mediated by the phosphoinositide 3-kinase/Akt cascade in synaptic plasticity and memory in the rat. Eur J Neurosci 2006;23;3375-84.

Chiang HC, Wang L, Xie Z, Yau A, Zhong Y. PI3 kinase signaling is involved in Abeta-induced memory loss in Drosophila. Proc Natl Acad Sci USA 2010;107:7060-5.

Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Butterfield DA, Stella AM. Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat Rev Neurosci 2007;8:766-75.

Akter K, Lanza EA, Martin SA, Myronyuk N, Rua M, Raffa RB. Diabetes mellitus and Alzheimer's disease: shared pathology and treatment. Br J Clin Pharmacol 2011;71:365-76.

Karen R, Craig WR, Kristine Y, Ingmar S, Nikolaos S. Is late-onset Alzheimer’s disease really a disease of midlife? Alzheimer’s Dementia 2015;1:122-30.

Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K. Midlife cardiovascular risk factors and risk of dementia in late life. Neurology 2005;64:277-81.

Solomon A, Kareholt I, Ngandu T, Winblad B, Tuomilehto J, Soininen H, et al. Serum cholesterol changes after midlife and late-life cognition: twenty-one-year follow-up study. Neurology 2007;68:751-6.

Rea TD, Breitner JC, Psaty BM, Fitzpatrick AL, Lopez OL, Newman AB, et al. Statin use and the risk of incident dementia: the cardiovascular health study. Arch Neurol 2005;62:1047-51.

Zandi PP, Sparks DL, Khachaturian AS, Khachaturian AS, Tschanz J, Norton M, et al. Do statins reduce the risk of incident dementia and Alzheimer disease? The cache county study. Arch Gen Psychiatry 2005;62:217-24.

Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, et al. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the cache county study. Arch Neurol 2004;61:82-8.

Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C, Dartigues JF, et al. Dietary patterns and risk of dementia: the three-city cohort study. Neurology 2007;69:1921-30.

Laitinen MH, Ngandu T, Rovio S, Helkala EL, Uusitalo U, Viitanen M, et al. Fat intake at midlife and risk of dementia and Alzheimer’s disease: a population based study. Dementia Geriatr Cognit Disord 2006;22:99-107.

Clark TA, Lee HP, Rolston RK. Oxidative stress and its implications for future treatments and management of Alzheimer disease. Int J Biomed Sci 2010;6:225-7.

Ono K, Yamada M. Vitamin A and Alzheimer’s disease. Geriatrics Gerontol Int 2012;12:180-8.

Lawlor DA, Smith GD, Kundu D, Bruckdorfer KR, Ebrahim S. Those confounded vitamins: what can we learn from the differences between observational versus randomized trial evidence? Lancet 2004;363:1724-7.

Fratiglioni L, Paillard-Borg S, Winblad B. An active and socially integrated lifestyle in late life might protect against dementia. Lancet Neurol 2004;3:343-53.

Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol 2011;10:819-28.

Qiu C, Bäckman L, Winblad B, Agüero-Torres H, Fratiglioni L. The influence of education on clinically diagnosed dementia: incidence and mortality data from the kungsholmen project. Arch Neurol 2001;58:2034-9.

Ngandu T, Von Strauss E, Helkala EL, Winblad B, Nissinen A, Tuomilehto J, et al. Education and dementia: what lies behind the association? Neurology 2007;69:1442-50.

Fratiglioni L, Wang HX, Ericsson K, Maytan M, Winblad B. Influence of social network on occurrence of dementia: a community-based longitudinal study. Lancet 2000;355:1315-9.

Wang HX, Karp A, Herlitz A, Crowe M, Kareholt I, Winblad B, et al. Personality and lifestyle in relation to dementia incidence. Neurology 2009;72:253-9.

Wang HX, Karp A, Winblad B, Fratiglioni L. Late-life engagement in social and leisure activities is associated with a decreased risk of dementia: a longitudinal study from the Kungsholmen project. Am J Epidemiol 2002;155:1081-7.

Serrani D. Narcissism vulnerability as a risk factor for Alzheimer´s disease-a prospective study. Austin J Clin Neurol 2015;2:1057.

Saczynski JS, Pfeifer LA, Masaki K, Korf ES, Laurin D, White L, et al. The effect of social engagement on incident dementia: the honolulu-asia aging study. Am J Epidemiol 2006;163:433-40.

Lee Y. Systematic review of health behavioral risks and cognitive health in older adults. Int Psychogeriatrics 2010;22:174.

Crowe M, Andel R, Pedersen NL, Johansson B, Gatz M. Does participation in leisure activities lead to reduced risk of Alzheimer’s disease? A prospective study of swedish twins. J Gerontol B Psychol Sci Soc Sci 2003;58:249-55.

Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol 2006;5:64-74.

Valenzuela MJ, Sachdev P, Wen W, Chen X, Brodaty H. Lifespan mental activity predicts diminished rate of hippocampal atrophy. PLoS One 2008;3:2598.

Reddy PH, Beal MF. Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer’s disease. Trends Mol Med 2008;14:45–53.

Butterfield DA, Boyd-Kimball D. The critical role of methionine 35 in Alzheimer’s amyloid ð›½-peptide (1-42)-induced oxidative stress and neurotoxicity. Biochim Biophys Acta 2005;1703:149-56.

Nelson PT, Alafuzoff I, Bigio EH, Bouras C, Braak H, Cairns NJ, et al. Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol 2012;71:362–81.

Karen C, Edward HK. Emerging therapeutics for Alzheimer’s disease in Insel, Amara, Blaschkeed. Ann Rev Pharmacol Toxicol 2014;54:381-406.

Rapoport SI. Coupled reductions in brain oxidative phosphorylation and synaptic function can be quantified and staged in the course of Alzheimer disease. Neurotoxic Res 2003;5:385-97.

Lasagna-Reeves CA, Castillo-Carranza DL, Sengupta U, Clos AL, Jackson GR, Kayed R. Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice. Mol Neurodegener 2011;6:39.

Hyman BT. Amyloid-dependent and amyloid-independent stages of Alzheimer disease. Arch Neurol 2011;68:1062-4.

Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 2002;297:353-6.

Mahley RW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 1988;240:622-30.

Hatters DM, Peters-Libeu CA, Weisgraber KH. Apolipoprotein E structure: insights into function. Trends Biochem Sci 2006;31:445-54.

Ye S, Huang Y, Mullendorff K, Dong L, Giedt G, Meng EC, et al. Apolipoprotein (apo) E4 enhance amyloid-β peptide production in cultured neuronal cells: ApoE structure as a potential therapeutic target. Proc Natl Acad Sci USA 2005;102:18700-5.

Crehan H, Hardy J, Pocock J. Microglia, Alzheimer’s disease, and complement. Int J Alzheimer’s Disase 2012:9:836-40.

Enns GM, Kinsman SL, Perlman SL, Spicer KM, Abdenur JE, et al. Initial experience in the treatment of inherited mitochondrial disease with EPI-743. Mol Genet Metab 2012;105:91-102.

Lovell MA, Ehmann WD, Butler SM, Markesbery WR. Elevated thiobarbituric acid reactive substances and antioxidant enzyme activity in the brain in Alzheimer's disease. Neurology 1995;45:1594-601.

Markesbery WR, Lovell MA. Four-hydroxy nonanal, a product of lipid peroxidation, is increased in the brain in Alzheimer's disease. Neurobiol Aging 1998;19:33-6.

Montine KS, Reich E, Neely MD, Sidell KR, Olson SJ, Markesbery WR, et al. Distribution of reducible 4-hydroxynonenal adduct immunoreactivity in Alzheimer disease is associated with APOE genotype. J Neuropathol Exp Neurol 1998;57:415-25.

Lu T, Aron L, Zullo J, Pan Y, Kim H, Chen Y, et al. REST and stress resistance in aging and Alzheimer’s disease. Nature 2014;507:448-54.

Jomova K, Vondrakova D, Lawson M, Valko M. Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem 2010;345:91-104.

Hensley K, Hall N, Subramaniam R, Cole P, Harris M, Aksenov M, et al. Brain regional correspondence between Alzheimer's disease histopathology and biomarkers of protein oxidation. J Neurochem 1995;65:2146-56.

Aksenov MY, Aksenova MV, Butterfield DA, Geddes JW, Markesbery WR. Protein oxidation in the brain in Alzheimer's disease. Neuroscience 2001;103:373-83.

Anderson AJ, Su JH, Cotman CW. DNA damage and apoptosis in Alzheimer's disease: colocalization with c-Jun immune-reactivity, relationship to brain area, and effect of postmortem delay. J Neurosci 1996;16:1710-9.

Mullaart E, Boerrigter ME, Ravid R, Swaab DF, Vijg J. Increased levels of DNA breaks in the cerebral cortex of Alzheimer's disease patients. Neurobiol Aging 1990;11:169-73.

Foy CJ, Passmore AP, Vahidassr MD, Young IS, Lawson JT. Plasma chain breaking antioxidants in Alzheimer's disease, vascular dementia and Parkinson's disease. Q J Med 1999;92:39-45.

Kim TS, Pae CU, Yoon SJ, Lee NJ, Kim JJ, Lee SJ, et al. Decreased plasma antioxidants in patients with Alzheimer's disease. Int J Geriatric Psychiatry 2006;21:344-8.

Alejandro Gella, Nuria Durany. Oxidative stress in Alzheimer disease. Cell Adhesion Migration 2009;3:1, 88-93.

Karbowski M. Mitochondria on guard: role of mitochondrial fusion and fission in the regulation of apoptosis. Adv Exp Med Biol 2010;687:131–42.

Castellani R, Hirai K, Aliev G, Drew KL, Nunomura A, Takeda A, et al. Role of mitochondrial dysfunction in Alzheimer's disease. J Neurosci Res 2002;70:357-60.

Gibson GE, Sheu KF, Blass JP. Abnormalities of mitochondrial enzymes in Alzheimer disease. J Neural Transm 1998;105:855-70.

Wang X, Su B, Zheng L, Perry G, Smith MA, Zhu X. The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer's disease. J Neurochem 2009;109:153-9.

Schmitt K, Grimm A, Kazmierczak A, Strosznajder JB, otz JG, Eckert A. Insights into mitochondrial dysfunction: aging, amyloid-ð›½, and tau-A deleterious trio. Antioxid Redox Signaling 2012;16:1456-66.

Moreira PI, Carvalho C, Zhu X, Smith MA, Perry G. Mitochondrial dysfunction is a trigger of Alzheimer’s disease pathophysiology. Biochim Biophys Acta 2010;1802:2-10.

Hauptmann S, Scherping I, Drose S, Brandt U, Schulz KL, Jendrach M, et al. Mitochondrial dysfunction: an early event in Alzheimer pathology accumulates with age in AD transgenic mice. Neurobiol Aging 2009;30:1574-86.

Gibson GE, Chen HL, Xu H, Qiu L, Xu Z, Denton TT, et al. Deficits in the mitochondrial enzyme alpha-ketoglutarate dehydrogenase leads to Alzheimer’s disease like calcium dysregulation. Neurobiol Aging 2012;33:1113-24.

Peterson C, Gibson GE, Blass JP. Altered calcium uptake in cultured skin fibroblasts from patients with Alzheimer's disease. N Engl J Med 1985;312:1063-5.

Ito E, Oka K, Etcheberrigaray R, Nelson TJ, McPhie DL, Tofel-Grehl B, et al. Internal Ca2+mobilization is altered in fibroblasts from patients with Alzheimer disease. Proc Natl Acad Sci USA 1994;91:534-8.

Olichon A, Landes T, Arnaune-Pelloquin L, Emorine LJ, Mils V, Guichet A, et al. Effects of OPA1 mutations on mitochondrial morphology and apoptosis: relevance to ADOA pathogenesis. J Cell Physiol 2007;211:423–30.

Perry EK, Perry RH, Tomlinson BE. Coenzyme a acetylating enzymes in Alzheimer’s disease: possible cholinergic compartment of pyruvate dehydrogenase. Neurosci Lett 1980;18:105-10.

Gibson GE, Sheu KF, Blass JP. Abnormalities of mitochondrial enzymes in Alzheimer disease. J Neural Transm 1998;105:855-70.

Chandrasekaran K, Giordano T, Brady DR, Stoll J, Martin LJ, Rapoport SI. Impairment in mitochondrial cytochrome oxidase gene expression in Alzheimer disease. Brain Res Mol Brain Res 1994;24:336-40.

Cottrell DA, Blakely EL, Johnson MA, Ince PG, Turnbull DM. Mitochondrial enzyme-deficient hippocampal neurons and choroidal cells in AD. Neurology 2001;57:260-4.

Maurer I, Zierz S, Moller HJ. A selective defect of cytochrome c oxidase is present in the brain of Alzheimer disease patients. Neurobiol Aging 2000;21:455-62.

Nagy Z, Esiri MM, LeGris M, Matthews PM. Mitochondrial enzyme expression in the hippocampus in relation to Alzheimer-type pathology. Acta Neuropathol 1999;97:346-54.

Parker WD, Mahr NJ, Filley CM, Parks JK, Hughes D, Young DA, et al. Reduced platelet cytochrome c oxidase activity in Alzheimer's disease. Neurology 1994;44:1086-90.

Ko LW, Sheu KFR, Thaler HT, Markesbery WR, Blass JP. Selective loss of KGDHC-enriched neurons in Alzheimer temporal cortex: does mitochondrial variation contribute to selective vulnerability? J Mol Neurosci 2001;17:361-9.

Perry EK. The cholinergic hypothesis ten years on. Br Med Bull 1986;42:63-9.

Lyketsos CG, Carrillo MC, Ryan JM. Neuropsychiatric symptoms in Alzheimer’s disease. Alzheimer’s Dementia 2011;7:532-9.

Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 y. J Neuropathol Exp Neurol 2011;70:960-9.

Beach TG, Monsell SE, Phillips LE, Kukull W. Accuracy of the clinical diagnosis of Alzheimer disease at the national institute on aging Alzheimer disease centers. J Neuropathol Exp Neurol 2012;71:266-73.

Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, Dekosky ST. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Neurology 2001;56:1133-42.

Knopman DS, Dekosky ST, Cummings JL. Practice parameter: diagnosis of dementia (an evidenced-based review). Neurology 2001;56:1143-53.

Doody RS, Stevens JC, Beck C. Practice parameter: management of dementia (an evidenced-based review). Neurology 2001;56:1154-66.

Salomone S, Caraci F, Leggio GM, Fedotova J, Drago F. New pharmacological strategies for treatment of Alzheimer’s disease: focus on disease modifying drugs. Br J Clin Pharmacol 2012;73:504-17.

Panza F, Frisardi V, Imbimbo BP, Seripa D, Paris F, Santamato A, et al. Anti-β-amyloid immunotherapy for Alzheimer’s disease: focus on bapineuzumab. Curr Alzheimer Res 2011;8:808-17.

Aprahamian I, Florindo S, Orestes, Forlenza V. New treatment strategies for Alzheimer’s disease: is there hope? Indian J Med Res 2013;449-60.

Bolognesi ML, Bartolini M, Tarozzi A, Morroni F, Lizzi F, Milelli A, et al. Multitargeted drugs discovery: balancing anti-amyloid and anticholinesterase capacity in a single chemical entity. Bioorg Med Chem Lett 2011;21:2655-8.

Nagaraja Prasad S, Jagadeesh K, Vedavathi H, Shreenivas P. Alzheimer disease: therapeutic targets and recent developments in treatment. Sch Acad J Pharm 2015;4:222-5.

Wiessner C, Wiederhold KH, Tissot AC, Frey P, Danner S, Jacobson LH, et al. The second-generation active Aβ immunotherapy CAD106 reduces amyloid accumulation in APP transgenic mice while minimizing potential side effects. J Neurosci 2011;31:9323-31.

Landen JW, Zhao Q, Cohen S, Borrie M, Woodward M, Billing CB, et al. Safety and pharmacology of a single intravenous dose of ponezumab in subjects with mild-to-moderate Alzheimer disease: a phase I, randomized, placebo-controlled, double-blind, dose-escalation study. Clin Neuropharmacol 2013;36:14-23.

Burstein AH, Zhao Q, Ross J, Styren S, Landen JW, Ma WW, et al. Safety and pharmacology of ponezumab (PF-04360365) after a single 10-minute intravenous infusion in subjects with mild to moderate Alzheimer disease. Clin Neuropharmacol 2013;36:8-13.

Barakos J, Carlson C, Estergard W, Oh J, Suhy J, Jack CR, et al. Vasogenic edema in the setting of β-amyloid lowering therapy, adverse event: what is it and how is it detected? Alzheimers Dement 2011;7(Suppl):75.

Chang WP, Huang X, Downs D, Cirrito JR, Koelsch G, Holtzman DM, et al. Beta-secretase inhibitor GRL-8234 rescues age-related cognitive decline in APP transgenic mice. FASEB J 2011;25:775-84.

Hamada Y, Kiso Y. Advances in the identification of β-secretase inhibitors. Expert Opin Drug Discovery 2013;8:709-31.

Sivilia S, Lorenzini L, Giuliani A, Gusciglio M, Fernandez M, Baldassarro VA, et al. Multitarget action of the novel anti-Alzheimer compound CHF5074: in vivo study of long-term treatment in T-2576 mice. BMC Neurosci 2013;14:44.

Vassar R, Bennett BD, Babu-Khan S. ð›½-Secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 1999;286:735-41.

Yan R, Blenkowski MJ, Shuck ME. Membrane anchored aspartyl protease with Alzheimer’s disease ð›½-secretase activity. Nature1999;402:533-7.

Michalik L, Auwerx J, Berger JP. International union of pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev 2006;58:726-41.

Mandrekar-Colucci S, Colleen Karlo J, Landreth GE. Mechanisms underlying the rapid peroxisome proliferator activated receptor-γ mediated amyloid clearance and reversal of cognitive deficits in a murine model of Alzheimer’s disease. J Neurosci 2012;32:10117-28.

Landreth G, Jiang Q, Mandrekar S, Heneka M. PPAR agonists as therapeutics for the treatment of Alzheimer’s disease. Neurotherapeutics 2008;5:481-9.

Craft S. The role of metabolic disorders in Alzheimer disease and vascular dementia: two roads converged. Arch Neurol 2009;66:300-5.

Shoji M, Golde TE, Ghiso J. Production of the Alzheimer amyloid 𛽠protein by normal proteolytic processing. Science 1992;258:126-9.

Haass C, Schlossmacher MG, Hung AY, Vigo-Pelfrey C, Mellon A, Ostaszewski BL, et al. Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature 1992;359:322-5.

Borgegcard T, Gustavsson S, Nilsson C. Alzheimers disease: presenilin 2-sparing γ-secretase inhibition is a tolerable peptide-lowering strategy. J Neurosci 2012;32:17297-305.

Zhao B, Yu M, Neitzel M, Marugg J, Jagodzinski J, Lee M, et al. Identification of γ-secretase inhibitor potency determinants on presenilin. J Biol Chem 2008;283:2927-38.

Crump CJ, Castro SV, Wang F, Pozdnyakov N, Ballard TE, Sisodia SS, et al. BMS-708,163 targets presenilin and lacks notch-sparing activity. Biochemistry 2012;51:7209-11.

Pei JJ, Ogren MS, Winblad B. Neurofibrillary degeneration in Alzheimer’s disease: from molecular mechanisms to identification of drug targets. Curr Opinion Psychiatry 2008;21:555-61.

QiutianJia, Yulin Deng, Hong Qing. Potential therapeutic strategies for Alzheimer’s disease targeting or beyond ð›½-Amyloid: Insights from clinical trials. Bio Med Res Int 2014. doi.org/10.1155/2014/837157. [Article in Press]

Seren L, Coma M, Rodr M, Guez L. A novel GSK-3α inhibitor reduces Alzheimer’s pathology and rescues neuronal loss in vivo. Neurobiol Dis 2009;35:359-67.

Hurtado DE, Molina-Porcel L, Iba M. A𛽠accelerates the spatiotemporal progression of tau pathology and augments tau amyloidosis in an Alzheimer mouse model. Am J Pathol 2010;177:1977-88.

Zhang B, Carroll J, Trojanowski JQ. The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer's-like pathology in an interventional study with aged tau transgenic mice. J Neurosci 2012;32:3601-11.

Swerdlow RH, Khan SM. A mitochondrial cascade hypothesis for sporadic Alzheimer’s disease. Med Hypotheses 2004; 63:8–20.

Doody RS, Gavrilova SI, Sano M, Thomas RG, Aisen PS, Bachurin SO, et al. Effect of dimebon on cognition, activities of daily living, behavior, and global function in patients with mild-to-moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled study. Lancet 2008;372:207-15.

Tariot P, Sabbagh M, Flitman S, Reyes P, Taber L, andSeely L. A safety, tolerability and pharmacokinetic study of dimebon in patients with Alzheimer’s disease already receiving donepezil. Alzheimer’s Dementia 2009;5:P251.

Reiman EM, Chen K, Alexander GE. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proc Natl Acad Sci USA 2004; 101:284-9.

Nordberg A, Darreh-Shori T, Svenson A, Guan Z. AChE and BuChE activities in CSF of mild AD patients following 12 mo of rivastigmine treatment. J Neurol Sci 2001;187:P0144.

Hampel H. Current insights into the pathophysiology of Alzheimer’s disease: selecting targets for early therapeutic intervention. Int Psychogeriatr 2012;24(Suppl 1):S10-7.

Salomone S, Caraci F, Leggio GM, Fedotova J, Drago F. New pharmacological strategies for treatment of Alzheimer’s disease: focus on disease modifying drugs. Br J Clin Pharmacol 2012;73:504-17.

Hanger DP, Anderton BH, Noble W. Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol Med 2009;15:112-9.

Published

01-02-2016

How to Cite

Kaur, K., R. Kaur, and M. Kaur. “RECENT ADVANCES IN ALZHEIMER’S DISEASE: CAUSES AND TREATMENT”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 8, no. 2, Feb. 2016, pp. 8-15, https://journals.innovareacademics.in/index.php/ijpps/article/view/8750.

Issue

Section

Review Article(s)