Understanding the pathophysiology of alzheimer's disease
Insights for early diagnosis
Keywords:
alzheimer's disease, neurodegeneration, amyloid-beta, biomarkers, nanotechnology, therapeutic interventionsAbstract
Background: Neurodegenerative diseases, particularly Alzheimer's disease (AD), pose a significant health challenge globally, with projections indicating nearly 152 million affected individuals by 2050. AD accounts for 60% to 80% of neurodegenerative cases, manifesting primarily as sporadic Alzheimer's disease (SAD) after age 65. Aim: This review aims to elucidate the pathophysiology of AD, focusing on the early identification of biomarkers for diagnosis and the exploration of potential therapeutic interventions. Methods: A comprehensive literature review was conducted, examining the biological mechanisms underpinning AD, particularly the role of amyloid plaques and neurofibrillary tangles, along with the impact of lipid nutrients and nanotechnology in treatment delivery. Results: Key findings indicate that soluble amyloid-beta oligomers are critical in AD pathogenesis, contributing to synaptic dysfunction and cognitive decline. Moreover, recent advancements in nanotechnology, particularly through nanoliposomes, show promise for enhancing drug delivery across the blood-brain barrier. Conclusion: Understanding the complex interplay of genetic, environmental, and pathological factors in AD can inform early diagnostic strategies and therapeutic approaches. The role of lifestyle and dietary interventions is crucial, and future research should focus on leveraging nanotechnology for effective treatment delivery.
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Scheltens, P.; Blennow, K.; Breteler, M.M.B.; de Strooper, B.; Frisoni, G.B.; Salloway, S.; Van der Flier, W.M. Alzheimer’s Disease. Lancet 2016, 388, 505–517. DOI: https://doi.org/10.1016/S0140-6736(15)01124-1
Prince, M.J. World Alzheimer Report 2015: The Global Impact of Dementia. Available online: https://www.alz.co.uk/research/world-report-2015
Livingston, G.; Huntley, J.; Sommerlad, A.; Ames, D.; Ballard, C.; Banerjee, S.; Brayne, C.; Burns, A.; Cohen-Mansfield, J.; Cooper, C.; et al. Dementia Prevention, Intervention, and Care: 2020 Report of the Lancet Commission. Lancet 2020, 396, 413–446. DOI: https://doi.org/10.1016/S0140-6736(20)30367-6
Alzheimer’s Association. 2018 Alzheimer’s Disease Facts and Figures. Alzheimer’s Dement. 2018, 14, 367–429. DOI: https://doi.org/10.1016/j.jalz.2018.02.001
Thal, D.R.; Rüb, U.; Orantes, M.; Braak, H. Phases of Aβ-Deposition in the Human Brain and Its Relevance for the Development of AD. Neurology 2002, 58, 1791–1800. DOI: https://doi.org/10.1212/WNL.58.12.1791
Braak, H.; Braak, E. Neuropathological Stageing of Alzheimer-Related Changes. Acta Neuropathol. 1991, 82, 239–259. DOI: https://doi.org/10.1007/BF00308809
Knopman, D.S.; Amieva, H.; Petersen, R.C.; Chételat, G.; Holtzman, D.M.; Hyman, B.T.; Nixon, R.A.; Jones, D.T. Alzheimer Disease. Nat. Rev. Dis. Prim. 2021, 7, 33. DOI: https://doi.org/10.1038/s41572-021-00269-y
Wang, Z.-X.; Tan, L.; Liu, J.; Yu, J.-T. The Essential Role of Soluble Aβ Oligomers in Alzheimer’s Disease. Mol. Neurobiol. 2016, 53, 1905–1924. DOI: https://doi.org/10.1007/s12035-015-9143-0
Sengupta, U.; Nilson, A.N.; Kayed, R. The Role of Amyloid-β Oligomers in Toxicity, Propagation, and Immunotherapy. EBioMedicine 2016, 6, 42–49. DOI: https://doi.org/10.1016/j.ebiom.2016.03.035
Tolar, M.; Hey, J.; Power, A.; Abushakra, S. Neurotoxic Soluble Amyloid Oligomers Drive Alzheimer’s Pathogenesis and Represent a Clinically Validated Target for Slowing Disease Progression. Int. J. Mol. Sci. 2021, 22, 6355. DOI: https://doi.org/10.3390/ijms22126355
Hayden, E.Y.; Teplow, D.B. Amyloid β-Protein Oligomers and Alzheimer’s Disease. Alzheimer’s Res. Ther. 2013, 5, 60. DOI: https://doi.org/10.1186/alzrt226
Mucke, L. Neuroscience: Alzheimer’s Disease. Nature 2009, 461, 895–897. DOI: https://doi.org/10.1038/461895a
Mattson, M.P. Pathways towards and Away from Alzheimer’s Disease. Nature 2004, 430, 631–639. DOI: https://doi.org/10.1038/nature02621
Vickers, J.C.; Mitew, S.; Woodhouse, A.; Fernandez-Martos, C.M.; Kirkcaldie, M.T.; Canty, A.J.; McCormack, G.H.; King, A.E. Defining the Earliest Pathological Changes of Alzheimer’s Disease. Curr. Alzheimer Res. 2016, 13, 281–287. DOI: https://doi.org/10.2174/1567205013666151218150322
Villemagne, V.L.; Burnham, S.; Bourgeat, P.; Brown, B.; Ellis, K.A.; Salvado, O.; Szoeke, C.; Macaulay, S.L.; Martins, R.; Maruff, P.; et al. Amyloid β Deposition, Neurodegeneration, and Cognitive Decline in Sporadic Alzheimer’s Disease: A Prospective Cohort Study. Lancet Neurol. 2013, 12, 357–367. DOI: https://doi.org/10.1016/S1474-4422(13)70044-9
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5, 5th ed.; American Psychiatric Association: Washington, DC, USA, 2013; ISBN 978-0-89042-554-1. DOI: https://doi.org/10.1176/appi.books.9780890425596
Fish, P.V.; Steadman, D.; Bayle, E.D.; Whiting, P. New Approaches for the Treatment of Alzheimer’s Disease. Bioorganic Med. Chem. Lett. 2019, 29, 125–133. DOI: https://doi.org/10.1016/j.bmcl.2018.11.034
Cummings, J.; Fox, N. Defining Disease Modifying Therapy for Alzheimer’s Disease. J. Prev. Alzheimer’s Dis. 2017, 4, 109. DOI: https://doi.org/10.14283/jpad.2017.12
Andrieu, S.; Coley, N.; Lovestone, S.; Aisen, P.S.; Vellas, B. Prevention of Sporadic Alzheimer’s Disease: Lessons Learned from Clinical Trials and Future Directions. Lancet Neurol. 2015, 14, 926–944. DOI: https://doi.org/10.1016/S1474-4422(15)00153-2
Norton, S.; Matthews, F.E.; Barnes, D.E.; Yaffe, K.; Brayne, C. Potential for Primary Prevention of Alzheimer’s Disease: An Analysis of Population-Based Data. Lancet Neurol. 2014, 13, 788–794. DOI: https://doi.org/10.1016/S1474-4422(14)70136-X
Livingston, G.; Sommerlad, A.; Orgeta, V.; Costafreda, S.G.; Huntley, J.; Ames, D.; Ballard, C.; Banerjee, S.; Burns, A.; Cohen-Mansfield, J.; et al. Dementia Prevention, Intervention, and Care. Lancet 2017, 390, 2673–2734 DOI: https://doi.org/10.1016/S0140-6736(17)31363-6
Dubois, B.; Hampel, H.; Feldman, H.H.; Scheltens, P.; Aisen, P.; Andrieu, S.; Bakardjian, H.; Benali, H.; Bertram, L.; Blennow, K.; et al. Preclinical Alzheimer’s Disease: Definition, Natural History, and Diagnostic Criteria. Alzheimer’s Dement. 2016, 12, 292–323. DOI: https://doi.org/10.1016/j.jalz.2016.02.002
Spector, A.A. Essentiality of Fatty Acids. Lipids 1999, 34, S1–S3. DOI: https://doi.org/10.1007/BF02562220
Innis, S.M. Essential Fatty Acids in Growth and Development. Prog. Lipid Res. 1991, 30, 39–103. DOI: https://doi.org/10.1016/0163-7827(91)90006-Q
Kawakita, E.; Hashimoto, M.; Shido, O. Docosahexaenoic Acid Promotes Neurogenesis in Vitro and in Vivo. Neuroscience 2006, 139, 991–997 DOI: https://doi.org/10.1016/j.neuroscience.2006.01.021
Horrocks, L.A.; Farooqui, A.A. Docosahexaenoic Acid in the Diet: Its Importance in Maintenance and Restoration of Neural Membrane Function. Prostaglandins Leukot. Essent. Fat. Acids 2004, 70, 361–372. DOI: https://doi.org/10.1016/j.plefa.2003.12.011
Lu, C.-T.; Zhao, Y.-Z.; Wong, H.L.; Cai, J.; Peng, L.; Tian, X.-Q. Current Approaches to Enhance CNS Delivery of Drugs across the Brain Barriers. Int. J. Nanomed. 2014, 9, 2241 DOI: https://doi.org/10.2147/IJN.S61288
Saraiva, C.; Praça, C.; Ferreira, R.; Santos, T.; Ferreira, L.; Bernardino, L. Nanoparticle-Mediated Brain Drug Delivery: Overcoming Blood-Brain Barrier to Treat Neurodegenerative Diseases. J. Control. Release 2016, 235, 34–47. DOI: https://doi.org/10.1016/j.jconrel.2016.05.044
Cano, A.; Turowski, P.; Ettcheto, M.; Duskey, J.T.; Tosi, G.; Sánchez-López, E.; García, M.L.; Camins, A.; Souto, E.B.; Ruiz, A.; et al. Nanomedicine-Based Technologies and Novel Biomarkers for the Diagnosis and Treatment of Alzheimer’s Disease: From Current to Future Challenges. J. Nanobiotechnol. 2021, 19, 122. DOI: https://doi.org/10.1186/s12951-021-00864-x
Agrawal, M.; Ajazuddin; Tripathi, D.K.; Saraf, S.; Saraf, S.; Antimisiaris, S.G.; Mourtas, S.; Hammarlund-Udenaes, M.; Alexander, A. Recent Advancements in Liposomes Targeting Strategies to Cross Blood-Brain Barrier (BBB) for the Treatment of Alzheimer’s Disease. J. Control. Release 2017, 260, 61–77. DOI: https://doi.org/10.1016/j.jconrel.2017.05.019
Saint-Pol, J.; Gosselet, F.; Duban-Deweer, S.; Pottiez, G.; Karamanos, Y. Targeting and Crossing the Blood-Brain Barrier with Extracellular Vesicles. Cells 2020, 9, 851 DOI: https://doi.org/10.3390/cells9040851
Kaushik, A.; Jayant, R.D.; Bhardwaj, V.; Nair, M. Personalized Nanomedicine for CNS Diseases. Drug Discov. Today 2018, 23, 1007–1015. DOI: https://doi.org/10.1016/j.drudis.2017.11.010
Goldsmith, M.; Abramovitz, L.; Peer, D. Precision Nanomedicine in Neurodegenerative Diseases. ACS Nano 2014, 8, 1958–1965. [ DOI: https://doi.org/10.1021/nn501292z
Vieira, D.; Gamarra, L. Getting into the Brain: Liposome-Based Strategies for Effective Drug Delivery across the Blood-Brain Barrier. Int. J. Nanomed. 2016, 11, 5381–5414. DOI: https://doi.org/10.2147/IJN.S117210
Ross, C.; Taylor, M.; Fullwood, N.; Allsop, D. Liposome Delivery Systems for the Treatment of Alzheimer’s Disease. Int. J. Nanomed. 2018, 13, 8507–8522 DOI: https://doi.org/10.2147/IJN.S183117
Maherani, B.; Arab-Tehrany, E.; Mozafari, M.R.; Gaiani, C.; Linder, M. Liposomes: A Review of Manufacturing Techniques and Targeting Strategies. Available online: http://www.eurekaselect.com/73978/article
Khorasani, S.; Danaei, M.; Mozafari, M.R. Nanoliposome Technology for the Food and Nutraceutical Industries. Trends Food Sci. Technol. 2018, 79, 106–115. DOI: https://doi.org/10.1016/j.tifs.2018.07.009
Torchilin, V.P. Recent Advances with Liposomes as Pharmaceutical Carriers. Nat. Rev. Drug Discov. 2005, 4, 145–160. DOI: https://doi.org/10.1038/nrd1632
Sharma, D.; Ali, A.A.E.; Trivedi, L.R. An Updated Review On:Liposomes as Drug Delivery System. PharmaTutor 2018, 6, 50. DOI: https://doi.org/10.29161/PT.v6.i2.2018.50
Pattni, B.S.; Chupin, V.V.; Torchilin, V.P. New Developments in Liposomal Drug Delivery. Chem. Rev. 2015, 115, 10938–10966. DOI: https://doi.org/10.1021/acs.chemrev.5b00046
Kales, H.C.; Gitlin, L.N.; Lyketsos, C.G. Assessment and Management of Behavioral and Psychological Symptoms of Dementia. BMJ 2015, 350, h369. DOI: https://doi.org/10.1136/bmj.h369
Lanctôt, K.L.; Amatniek, J.; Ancoli-Israel, S.; Arnold, S.E.; Ballard, C.; Cohen-Mansfield, J.; Ismail, Z.; Lyketsos, C.; Miller, D.S.; Musiek, E.; et al. Neuropsychiatric Signs and Symptoms of Alzheimer’s Disease: New Treatment Paradigms. Alzheimer’s Dement. 2017, 3, 440–449. DOI: https://doi.org/10.1016/j.trci.2017.07.001
Cerejeira, J.; Lagarto, L.; Mukaetova-Ladinska, E.B. Behavioral and Psychological Symptoms of Dementia. Front. Neur. 2012, 3, 73. DOI: https://doi.org/10.3389/fneur.2012.00073
Finkel, S.I.; Costa e Silva, J.; Cohen, G.; Miller, S.; Sartorius, N. Behavioral and Psychological Signs and Symptoms of Dementia: A Consensus Statement on Current Knowledge and Implications for Research and Treatment. Int. Psychogeriatr. 1996, 8 (Suppl. 3), 497–500. DOI: https://doi.org/10.1017/S1041610297003943
Jack, C.R.; Knopman, D.S.; Jagust, W.J.; Shaw, L.M.; Aisen, P.S.; Weiner, M.W.; Petersen, R.C.; Trojanowski, J.Q. Hypothetical Model of Dynamic Biomarkers of the Alzheimer’s Pathological Cascade. Lancet Neurol. 2010, 9, 119–128. [ DOI: https://doi.org/10.1016/S1474-4422(09)70299-6
Giannakopoulos, P.; Herrmann, F.R.; Bussière, T.; Bouras, C.; Kövari, E.; Perl, D.P.; Morrison, J.H.; Gold, G.; Hof, P.R. Tangle and Neuron Numbers, but Not Amyloid Load, Predict Cognitive Status in Alzheimer’s Disease. Neurology 2003, 60, 1495–1500. DOI: https://doi.org/10.1212/01.WNL.0000063311.58879.01
Allinquant, B.; Clamagirand, C.; Potier, M.-C. Role of Cholesterol Metabolism in the Pathogenesis of Alzheimer’s Disease. Curr. Opin. Clin. Nutr. Metab. Care 2014, 17, 319–323. DOI: https://doi.org/10.1097/MCO.0000000000000069
Haass, C.; Selkoe, D.J. Soluble Protein Oligomers in Neurodegeneration: Lessons from the Alzheimer’s Amyloid β-Peptide. Nat. Rev. Mol. Cell Biol. 2007, 8, 101–112. DOI: https://doi.org/10.1038/nrm2101
Viola, K.L.; Klein, W.L. Amyloid β Oligomers in Alzheimer’s Disease Pathogenesis, Treatment, and Diagnosis. Acta Neuropathol. 2015, 129, 183–206. DOI: https://doi.org/10.1007/s00401-015-1386-3
Cline, E.N.; Bicca, M.A.; Viola, K.L.; Klein, W.L. The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade. J. Alzheimer’s Dis. 2018, 64, S567–S610. DOI: https://doi.org/10.3233/JAD-179941
Hampel, H.; Mesulam, M.-M.; Cuello, A.C.; Farlow, M.R.; Giacobini, E.; Grossberg, G.T.; Khachaturian, A.S.; Vergallo, A.; Cavedo, E.; Snyder, P.J.; et al. The Cholinergic System in the Pathophysiology and Treatment of Alzheimer’s Disease. Brain 2018, 141, 1917–1933. DOI: https://doi.org/10.1093/brain/awy132
Nixon, R.A. Amyloid Precursor Protein and Endosomal-lysosomal Dysfunction in Alzheimer’s Disease: Inseparable Partners in a Multifactorial Disease. FASEB J. 2017, 31, 2729–2743. DOI: https://doi.org/10.1096/fj.201700359
Martins, I.J.; Hone, E.; Foster, J.K.; Sünram-Lea, S.I.; Gnjec, A.; Fuller, S.J.; Nolan, D.; Gandy, S.E.; Martins, R.N. Apolipoprotein E, Cholesterol Metabolism, Diabetes, and the Convergence of Risk Factors for Alzheimer’s Disease and Cardiovascular Disease. Mol. Psychiatry 2006, 11, 721–736. DOI: https://doi.org/10.1038/sj.mp.4001854
Zetterberg, H.; Mattsson, N. Understanding the Cause of Sporadic Alzheimer’s Disease. Expert Rev. Neurother. 2014, 14, 621–630. DOI: https://doi.org/10.1586/14737175.2014.915740
Hardy, J.; Higgins, G. Alzheimer’s Disease: The Amyloid Cascade Hypothesis. Science 1992, 256, 184–185. DOI: https://doi.org/10.1126/science.1566067
Jack, C.R.; Knopman, D.S.; Jagust, W.J.; Petersen, R.C.; Weiner, M.W.; Aisen, P.S.; Shaw, L.M.; Vemuri, P.; Wiste, H.J.; Weigand, S.D.; et al. Tracking Pathophysiological Processes in Alzheimer’s Disease: An Updated Hypothetical Model of Dynamic Biomarkers. Lancet Neurol. 2013, 12, 207–216. DOI: https://doi.org/10.1016/S1474-4422(12)70291-0
Knopman, D.S.; Jack, C.R.; Wiste, H.J.; Weigand, S.D.; Vemuri, P.; Lowe, V.J.; Kantarci, K.; Gunter, J.L.; Senjem, M.L.; Mielke, M.M.; et al. Brain Injury Biomarkers Are Not Dependent on β-Amyloid in Normal Elderly. Ann. Neurol. 2013, 73, 472–480. DOI: https://doi.org/10.1002/ana.23816
Chételat, G. Alzheimer Disease: Aβ-Independent Processes-Rethinking Preclinical AD. Nat. Rev. Neurol. 2013, 9, 123–124. DOI: https://doi.org/10.1038/nrneurol.2013.21
Mesulam, M.-M. Cholinergic Circuitry of the Human Nucleus Basalis and Its Fate in Alzheimer’s Disease: Human Cholinergic Circuitry. J. Comp. Neurol. 2013, 521, 4124–4144. DOI: https://doi.org/10.1002/cne.23415
Schliebs, R.; Arendt, T. The Cholinergic System in Aging and Neuronal Degeneration. Behav. Brain Res. 2011, 221, 555–563. DOI: https://doi.org/10.1016/j.bbr.2010.11.058
Francis, P.T. The Interplay of Neurotransmitters in Alzheimer’s Disease. CNS Spectr. 2005, 10, 6– DOI: https://doi.org/10.1017/S1092852900014164
Beach, T.G.; Kuo, Y.-M.; Spiegel, K.; Emmerling, M.R.; Sue, L.I.; Kokjohn, K.; Roher, A.E. The Cholinergic Deficit Coincides with Aβ Deposition at the Earliest Histopathologic Stages of Alzheimer Disease. J. Neuropathol. Exp. Neurol. 2000, 59, 308–313. DOI: https://doi.org/10.1093/jnen/59.4.308
Kang, S.; Lee, Y.; Lee, J.E. Metabolism-Centric Overview of the Pathogenesis of Alzheimer’s Disease. Yonsei Med. J. 2017, 58, 479–488. DOI: https://doi.org/10.3349/ymj.2017.58.3.479
Chételat, G.; Arbizu, J.; Barthel, H.; Garibotto, V.; Law, I.; Morbelli, S.; van de Giessen, E.; Agosta, F.; Barkhof, F.; Brooks, D.J.; et al. Amyloid-PET and 18F-FDG-PET in the Diagnostic Investigation of Alzheimer’s Disease and Other Dementias. Lancet Neurol. 2020, 19, 951–962. DOI: https://doi.org/10.1016/S1474-4422(20)30314-8
McKhann, G.; Drachman, D.; Folstein, M.; Katzman, R.; Price, D.; Stadlan, E.M. Clinical Diagnosis of Alzheimer’s Disease: Report of the NINCDS-ADRDA Work Group* under the Auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984, 34, 939. DOI: https://doi.org/10.1212/WNL.34.7.939
Albert, M.S.; DeKosky, S.T.; Dickson, D.; Dubois, B.; Feldman, H.H.; Fox, N.C.; Gamst, A.; Holtzman, D.M.; Jagust, W.J.; Petersen, R.C.; et al. The Diagnosis of Mild Cognitive Impairment Due to Alzheimer’s Disease: Recommendations from the National Institute on Aging-Alzheimer’s Association Workgroups on Diagnostic Guidelines for Alzheimer’s Disease. Alzheimer’s Dement. 2011, 7, 270–279. DOI: https://doi.org/10.1016/j.jalz.2011.03.008
McKhann, G.M.; Knopman, D.S.; Chertkow, H.; Hyman, B.T.; Jack, C.R.; Kawas, C.H.; Klunk, W.E.; Koroshetz, W.J.; Manly, J.J.; Mayeux, R.; et al. The Diagnosis of Dementia Due to Alzheimer’s Disease: Recommendations from the National Institute on Aging-Alzheimer’s Association Workgroups on Diagnostic Guidelines for Alzheimer’s Disease. Alzheimer’s Dement. 2011, 7, 263–269 DOI: https://doi.org/10.1016/j.jalz.2011.03.005
Dubois, B.; Feldman, H.H.; Jacova, C.; Hampel, H.; Molinuevo, J.L.; Blennow, K.; DeKosky, S.T.; Gauthier, S.; Selkoe, D.; Bateman, R.; et al. Advancing Research Diagnostic Criteria for Alzheimer’s Disease: The IWG-2 Criteria. Lancet Neurol. 2014, 13, 614–629. DOI: https://doi.org/10.1016/S1474-4422(14)70090-0
Jack, C.R.; Bennett, D.A.; Blennow, K.; Carrillo, M.C.; Dunn, B.; Haeberlein, S.B.; Holtzman, D.M.; Jagust, W.; Jessen, F.; Karlawish, J.; et al. NIA-AA Research Framework: Toward a Biological Definition of Alzheimer’s Disease. Alzheimer’s Dement. 2018, 14, 535–562. DOI: https://doi.org/10.1016/j.jalz.2018.02.018
Jack, C.R.; Holtzman, D.M. Biomarker Modeling of Alzheimer’s Disease. Neuron 2013, 80, 1347–1358. DOI: https://doi.org/10.1016/j.neuron.2013.12.003
Cummings, J. The National Institute on Aging-Alzheimer’s Association Framework on Alzheimer’s Disease: Application to Clinical Trials. Alzheimer’s Dement. 2019, 15, 172–178. DOI: https://doi.org/10.1016/j.jalz.2018.05.006
De Strooper, B.; Karran, E. The Cellular Phase of Alzheimer’s Disease. Cell 2016, 164, 603–615. DOI: https://doi.org/10.1016/j.cell.2015.12.056
Babiloni, C.; Lopez, S.; Del Percio, C.; Noce, G.; Pascarelli, M.T.; Lizio, R.; Teipel, S.J.; González-Escamilla, G.; Bakardjian, H.; George, N.; et al. Resting-State Posterior Alpha Rhythms Are Abnormal in Subjective Memory Complaint Seniors with Preclinical Alzheimer’s Neuropathology and High Education Level: The INSIGHT-PreAD Study. Neurobiol. Aging 2020, 90, 43–59. DOI: https://doi.org/10.1016/j.neurobiolaging.2020.01.012
Dubois, B.; Epelbaum, S.; Nyasse, F.; Bakardjian, H.; Gagliardi, G.; Uspenskaya, O.; Houot, M.; Lista, S.; Cacciamani, F.; Potier, M.-C.; et al. Cognitive and Neuroimaging Features and Brain β-Amyloidosis in Individuals at Risk of Alzheimer’s Disease (INSIGHT-PreAD): A Longitudinal Observational Study. Lancet Neurol. 2018, 17, 335–346. DOI: https://doi.org/10.1016/S1474-4422(18)30029-2
Soldan, A.; Pettigrew, C.; Cai, Q.; Wang, J.; Wang, M.-C.; Moghekar, A.; Miller, M.I.; Albert, M.; BIOCARD Research Team. Cognitive Reserve and Long-Term Change in Cognition in Aging and Preclinical Alzheimer’s Disease. Neurobiol. Aging 2017, 60, 164–172 DOI: https://doi.org/10.1016/j.neurobiolaging.2017.09.002
Lee, D.H.; Lee, P.; Seo, S.W.; Roh, J.H.; Oh, M.; Oh, J.S.; Oh, S.J.; Kim, J.S.; Jeong, Y. Neural Substrates of Cognitive Reserve in Alzheimer’s Disease Spectrum and Normal Aging. NeuroImage 2019, 186, 690–702. DOI: https://doi.org/10.1016/j.neuroimage.2018.11.053
Bachurin, S.O.; Gavrilova, S.I.; Samsonova, A.; Barreto, G.E.; Aliev, G. Mild Cognitive Impairment Due to Alzheimer Disease: Contemporary Approaches to Diagnostics and Pharmacological Intervention. Pharmacol. Res. 2018, 129, 216–226 DOI: https://doi.org/10.1016/j.phrs.2017.11.021
Roberts, R.; Knopman, D.S. Classification and Epidemiology of MCI. Clin. Geriatr. Med. 2013, 29, 753–772. DOI: https://doi.org/10.1016/j.cger.2013.07.003
Zhao, Q.-F.; Tan, L.; Wang, H.-F.; Jiang, T.; Tan, M.-S.; Tan, L.; Xu, W.; Li, J.-Q.; Wang, J.; Lai, T.-J.; et al. The Prevalence of Neuropsychiatric Symptoms in Alzheimer’s Disease: Systematic Review and Meta-Analysis. J. Affect. Disord. 2016, 190, 264–271. DOI: https://doi.org/10.1016/j.jad.2015.09.069
Jack, C.R.; Bennett, D.A.; Blennow, K.; Carrillo, M.C.; Feldman, H.H.; Frisoni, G.B.; Hampel, H.; Jagust, W.J.; Johnson, K.A.; Knopman, D.S.; et al. A/T/N: An Unbiased Descriptive Classification Scheme for Alzheimer Disease Biomarkers. Neurology 2016, 87, 539–547. DOI: https://doi.org/10.1212/WNL.0000000000002923
Atri, A. The Alzheimer’s Disease Clinical Spectrum. Med. Clin. North Am. 2019, 103, 263–293. DOI: https://doi.org/10.1016/j.mcna.2018.10.009
Barnes, D.E.; Yaffe, K. The Projected Effect of Risk Factor Reduction on Alzheimer’s Disease Prevalence. Lancet Neurol. 2011, 10, 819–828. DOI: https://doi.org/10.1016/S1474-4422(11)70072-2
Reitz, C.; Mayeux, R. Alzheimer Disease: Epidemiology, Diagnostic Criteria, Risk Factors and Biomarkers. Biochem. Pharmacol. 2014, 88, 640–651. DOI: https://doi.org/10.1016/j.bcp.2013.12.024
Deckers, K.; van Boxtel, M.P.J.; Schiepers, O.J.G.; de Vugt, M.; Muñoz Sánchez, J.L.; Anstey, K.J.; Brayne, C.; Dartigues, J.-F.; Engedal, K.; Kivipelto, M.; et al. Target Risk Factors for Dementia Prevention: A Systematic Review and Delphi Consensus Study on the Evidence from Observational Studies. Int. J. Geriatr. Psychiatry 2015, 30, 234–246. DOI: https://doi.org/10.1002/gps.4245
Silva, M.V.F.; Loures, C.d.M.G.; Alves, L.C.V.; de Souza, L.C.; Borges, K.B.G.; Carvalho, M.d.G. Alzheimer’s Disease: Risk Factors and Potentially Protective Measures. J. Biomed. Sci. 2019, 26, 33. DOI: https://doi.org/10.1186/s12929-019-0524-y
Lambert, J.C.; Ibrahim-Verbaas, C.A.; Harold, D.; Naj, A.C.; Sims, R.; Bellenguez, C.; DeStafano, A.L.; Bis, J.C.; Beecham, G.W.; Grenier-Boley, B.; et al. Meta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease. Nat. Genet. 2013, 45, 1452–1458.
Hebert, L.E.; Bienias, J.L.; Aggarwal, N.T.; Wilson, R.S.; Bennett, D.A.; Shah, R.C.; Evans, D.A. Change in Risk of Alzheimer Disease over Time. Neurology 2010, 75, 786–791. [ DOI: https://doi.org/10.1212/WNL.0b013e3181f0754f
Prince, M.J.; Guerchet, M.M.; Prina, M. The Epidemiology and Impact of Dementia: Current State and Future Trends. WHO Thematic Briefing. 2015. Available online: https://hal.archives-ouvertes.fr/hal-03517019
Bertram, L.; McQueen, M.B.; Mullin, K.; Blacker, D.; Tanzi, R.E. Systematic Meta-Analyses of Alzheimer Disease Genetic Association Studies: The AlzGene Database. Nat. Genet. 2007, 39, 17–23. DOI: https://doi.org/10.1038/ng1934
Loy, C.T.; Schofield, P.R.; Turner, A.M.; Kwok, J.B. Genetics of Dementia. Lancet 2014, 383, 828–840. DOI: https://doi.org/10.1016/S0140-6736(13)60630-3
Bekris, L.M.; Yu, C.-E.; Bird, T.D.; Tsuang, D.W. Review Article: Genetics of Alzheimer Disease. J. Geriatr. Psychiatry Neurol. 2010, 23, 213–227. DOI: https://doi.org/10.1177/0891988710383571
Karch, C.M.; Goate, A.M. Alzheimer’s Disease Risk Genes and Mechanisms of Disease Pathogenesis. Biol. Psychiatry 2015, 77, 43–51. DOI: https://doi.org/10.1016/j.biopsych.2014.05.006
Liu, Y.; Yu, J.-T.; Wang, H.-F.; Han, P.-R.; Tan, C.-C.; Wang, C.; Meng, X.-F.; Risacher, S.L.; Saykin, A.J.; Tan, L. APOE Genotype and Neuroimaging Markers of Alzheimer’s Disease: Systematic Review and Meta-Analysis. J. Neurol. Neurosurg. Psychiatry 2015, 86, 127–134. DOI: https://doi.org/10.1136/jnnp-2014-307719
Liu, C.-C.; Kanekiyo, T.; Xu, H.; Bu, G. Apolipoprotein E and Alzheimer Disease: Risk, Mechanisms and Therapy. Nat. Rev. Neurol. 2013, 9, 106–118. DOI: https://doi.org/10.1038/nrneurol.2012.263
Fisher, D.W.; Bennett, D.A.; Dong, H. Sexual Dimorphism in Predisposition to Alzheimer’s Disease. Neurobiol. Aging 2018, 70, 308–324. DOI: https://doi.org/10.1016/j.neurobiolaging.2018.04.004
Nebel, R.A.; Aggarwal, N.T.; Barnes, L.L.; Gallagher, A.; Goldstein, J.M.; Kantarci, K.; Mallampalli, M.P.; Mormino, E.C.; Scott, L.; Yu, W.H.; et al. Understanding the Impact of Sex and Gender in Alzheimer’s Disease: A Call to Action. Alzheimer’s Dement. 2018, 14, 1171–1183. DOI: https://doi.org/10.1016/j.jalz.2018.04.008
Riedel, B.C.; Thompson, P.M.; Brinton, R.D. Age, APOE and Sex: Triad of Risk of Alzheimer’s Disease. J. Steroid Biochem. Mol. Biol. 2016, 160, 134–147. DOI: https://doi.org/10.1016/j.jsbmb.2016.03.012
Whitmer, R.A.; Sidney, S.; Selby, J.; Johnston, S.C.; Yaffe, K. Midlife Cardiovascular Risk Factors and Risk of Dementia in Late Life. Neurology 2005, 64, 277–281. DOI: https://doi.org/10.1212/01.WNL.0000149519.47454.F2
Zlokovic, B.V. Neurovascular Pathways to Neurodegeneration in Alzheimer’s Disease and Other Disorders. Nat. Rev. Neurosci. 2011, 12, 723–738. DOI: https://doi.org/10.1038/nrn3114
Yu, J.-T.; Xu, W.; Tan, C.-C.; Andrieu, S.; Suckling, J.; Evangelou, E.; Pan, A.; Zhang, C.; Jia, J.; Feng, L.; et al. Evidence-Based Prevention of Alzheimer’s Disease: Systematic Review and Meta-Analysis of 243 Observational Prospective Studies and 153 Randomised Controlled Trials. J. Neurol. Neurosurg. Psychiatry 2020, 91, 1201–1209. DOI: https://doi.org/10.1136/jnnp-2019-321913
Edwards, G.A., III; Gamez, N.; Escobedo, G., Jr.; Calderon, O.; Moreno-Gonzalez, I. Modifiable Risk Factors for Alzheimer’s Disease. Front. Aging Neurosci. 2019, 11, 146. DOI: https://doi.org/10.3389/fnagi.2019.00146
Uauy, R.; Dangour, A.D. Nutrition in Brain Development and Aging: Role of Essential Fatty Acids. Nutr. Rev. 2006, 64, S24–S33, discussion S72–S91. DOI: https://doi.org/10.1301/nr.2006.may.S24-S33
Kao, Y.-C.; Ho, P.-C.; Tu, Y.-K.; Jou, I.-M.; Tsai, K.-J. Lipids and Alzheimer’s Disease. Int. J. Mol. Sci. 2020, 21, 1505. DOI: https://doi.org/10.3390/ijms21041505
Chew, H.; Solomon, V.A.; Fonteh, A.N. Involvement of Lipids in Alzheimer’s Disease Pathology and Potential Therapies. Front. Physiol. 2020, 11, 598. DOI: https://doi.org/10.3389/fphys.2020.00598
Korade, Z.; Kenworthy, A.K. Lipid Rafts, Cholesterol, and the Brain. Neuropharmacology 2008, 55, 1265–1273. DOI: https://doi.org/10.1016/j.neuropharm.2008.02.019
Luchsinger, J.A. Adiposity, Hyperinsulinemia, Diabetes and Alzheimer’s Disease. Eur. J. Pharmacol. 2008, 585, 119–129. DOI: https://doi.org/10.1016/j.ejphar.2008.02.048
Hildreth, K.L.; Pelt, R.E.; Schwartz, R.S. Obesity, Insulin Resistance, and Alzheimer’s Disease. Obesity 2012, 20, 1549–1557. DOI: https://doi.org/10.1038/oby.2012.19
Kandimalla, R.; Thirumala, V.; Reddy, P.H. Is Alzheimer’s Disease a Type 3 Diabetes? A Critical Appraisal. Biochim. Biophys. Acta-Mol. Basis Dis. 2017, 1863, 1078–1089. DOI: https://doi.org/10.1016/j.bbadis.2016.08.018
Thomas, J.; Thomas, C.J.; Radcliffe, J.; Itsiopoulos, C. Omega-3 Fatty Acids in Early Prevention of Inflammatory Neurodegenerative Disease: A Focus on Alzheimer’s Disease. Biomed. Res. Int. 2015, 2015, 172801. DOI: https://doi.org/10.1155/2015/172801
Zhu, T.-B.; Zhang, Z.; Luo, P.; Wang, S.-S.; Peng, Y.; Chu, S.-F.; Chen, N.-H. Lipid Metabolism in Alzheimer’s Disease. Brain Res. Bull. 2019, 144, 68–74. DOI: https://doi.org/10.1016/j.brainresbull.2018.11.012
Wong, M.W.; Braidy, N.; Poljak, A.; Pickford, R.; Thambisetty, M.; Sachdev, P.S. Dysregulation of Lipids in Alzheimer’s Disease and Their Role as Potential Biomarkers. Alzheimer’s Dement. 2017, 13, 810–827. DOI: https://doi.org/10.1016/j.jalz.2017.01.008
Justice, N.J. The Relationship between Stress and Alzheimer’s Disease. Neurobiol. Stress 2018, 8, 127–133. DOI: https://doi.org/10.1016/j.ynstr.2018.04.002
Ganguli, M.; Du, Y.; Dodge, H.H.; Ratcliff, G.G.; Chang, C.-C.H. Depressive Symptoms and Cognitive Decline in Late Life: A Prospective Epidemiological Study. Arch. Gen. Psychiatry 2006, 63, 153–160. [ DOI: https://doi.org/10.1001/archpsyc.63.2.153
Fleminger, S.; Oliver, D.L.; Lovestone, S.; Rabe-Hesketh, S.; Giora, A. Head Injury as a Risk Factor for Alzheimer’s Disease: The Evidence 10 Years on; a Partial Replication. J. Neurol. Neurosurg. Psychiatry 2003, 74, 857–862. DOI: https://doi.org/10.1136/jnnp.74.7.857
Peters, R.; Ee, N.; Peters, J.; Booth, A.; Mudway, I.; Anstey, K.J. Air Pollution and Dementia: A Systematic Review. J. Alzheimer’s Dis. 2019, 70, S145–S163. DOI: https://doi.org/10.3233/JAD-180631
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