A Survey of Genetic Risk Factors for Alzheimer’s Disease

Schachter, A. S., & Davis, K. L. (2000). Alzheimer’s disease. Dialogues in Clinical Neuroscience, 2(2), 91–100.https://doi.org/10.31887%2FDCNS.2000.2.2%2Fasschachter

(2023, April). 2023 Alzheimer’s Disease Facts and Figures [Review of 2023 Alzheimer’s Disease Facts and Figures]. Alzheimer’s Association. https://www.alz.org/media/documents/alzheimers-facts-and-figures.pdf

Bature, F., Guinn, B., Pang, D., et al. (2017). Signs and symptoms preceding the diagnosis of Alzheimer’s disease: a systematic scoping review of literature from 1937 to 2016. BMJ Open, 7(8), e015746. https://doi.org/10.1136%2Fbmjopen-2016-015746

Hampel, H., Hardy, J., Blennow, K., et al. (2021). The Amyloid-β Pathway in Alzheimer’s Disease. Molecular Psychiatry, 26(10). https://doi.org/10.1038/s41380-021-01249-0

Medeiros, R., Baglietto-Vargas, D., & LaFerla, F. M. (2010). The Role of Tau in Alzheimer’s Disease and Related Disorders. CNS Neuroscience & Therapeutics, 17(5), 514–524. https://doi.org/10.1111/j.1755-5949.2010.00177.x

Mendez, M. F. (2019). Early-onset Alzheimer disease and its variants. CONTINUUM: Lifelong Learning in Neurology, 25(1), 34–51. https://doi.org/10.1212/con.0000000000000687

National Institute of General Medical Sciences. (2017). What are genes? https://www.nigms.nih.gov/education/Documents/Studying_genes_final.pdf

Salzberg, S. L. (2018). Open questions: How many genes do we have? BMC Biology, 16(1). https://doi.org/10.1186/s12915-018-0564-x

Eichler, E. E. (2019). Genetic Variation, Comparative Genomics, and the Diagnosis of Disease. New England Journal of Medicine, 381(1), 64–74. https://doi.org/10.1056/nejmra1809315

Constitutional (germline) vs somatic (tumour) variants — Knowledge Hub. (n.d.). GeNotes. Retrieved June 19, 2023, from https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/constitutional-germline-vs-somatic-tumour-variants/#:~:text=Constitutional%20

Baptista, P. V. (2005). Principles in genetic risk assessment. Therapeutics and Clinical Risk Management, 1(1), 15–20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1661604/

National Institute on Aging. (2023, April 5). Alzheimer’s Disease Fact Sheet. National Institute on Aging. https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet

Moreno-Grau, S., Hernández, I., Heilmann-Heimbach, S., et al. (2018). Genome-wide significant risk factors on chromosome 19 and the APOE locus. Oncotarget, 9(37). https://doi.org/10.18632/oncotarget.25083

Frieden, C., Wang, H., & Ho, C. M. W. (2017). A mechanism for lipid binding to apoE and the role of intrinsically disordered regions coupled to domain–domain interactions. Proceedings of the National Academy of Sciences, 114(24), 6292–6297. https://doi.org/10.1073/pnas.1705080114

Frieden, C. (2014). ApoE: The role of conserved residues in defining function. Protein Science, 24(1), 138–144. https://doi.org/10.1002/pro.2597

Zhao, L., & Wu, L. (2016). ApoE2 and Alzheimer′s disease: time to take a closer look. Neural Regeneration Research, 11(3), 412. https://doi.org/10.4103/1673-5374.179044

goldmanb @stanford.edu, img src=’https://med stanford edu/news/media-contacts/bruce_goldman/_jcr_content/image img 620 high jpg/goldman-bruce-90 jpg’ alt=’Bruce G. B. G. B. G. is a science writer in the O. of C. E. him at. (n.d.). Gene variant staves off Alzheimer’s in some people. News Center. https://med.stanford.edu/news/all-news/2020/04/gene-variant-staves-off-alzheimers-in-some-people.html

Chiang, G. C., Insel, P. S., Tosun, D., et al. (2010). Hippocampal atrophy rates and CSF biomarkers in elderly APOE2 normal subjects(e–Pub ahead of print). Neurology, 75(22), 1976–1981. https://doi.org/10.1212/WNL.0b013e3181ffe4d1

Saeed, U., Desmarais, P., & Masellis, M. (2021). The APOE ε4 variant and hippocampal atrophy in Alzheimer’s disease and Lewy body dementia: a systematic review of magnetic resonance imaging studies and therapeutic relevance. Expert Review of Neurotherapeutics, 21(8), 851–870. https://doi.org/10.1080/14737175.2021.1956904

Osuntokun, B. O., Sahota, A., Ogunniyi, A. O., et al. (1995). Lack of an association between apolipoprotein E epsilon 4 and Alzheimer’s disease in elderly Nigerians. Annals of Neurology, 38(3), 463–465. https://doi.org/10.1002/ana.410380319

Petrikova, I., Bhattacharjee, R., & Fraser, P. D. (2023). The “Nigerian diet” and Its Evolution: Review of the Existing Literature and Household Survey Data. Foods, 12(3), 443. https://doi.org/10.3390/foods12030443

Rudajev, V., & Novotny, J. (2022). Cholesterol as a key player in amyloid β-mediated toxicity in Alzheimer’s disease. Frontiers in Molecular Neuroscience, 15. https://doi.org/10.3389/fnmol.2022.937056

Puglielli, L., Tanzi, R. E., & Kovacs, D. M. (2003). Alzheimer’s disease: the cholesterol connection. Nature Neuroscience, 6(4), 345–351. https://doi.org/10.1038/nn0403-345

Petanceska, S. S., DeRosa, S., Sharma, A., et al. (2003). Changes in apolipoprotein E expression in response to dietary and pharmacological modulation of cholesterol. Journal of Molecular Neuroscience: MN, 20(3), 395–406. https://doi.org/10.1385/JMN:20:3:395

Kim, J.-H., Hwang, K.-H., Park, K.-S., et al. (2015). Biological Role of Anti-aging Protein Klotho. Journal of Lifestyle Medicine, 5(1), 1–6. https://doi.org/10.15280/jlm.2015.5.1.1

Samsamshariat, S., Hasannejad, M., Esmaili, A., et al. (2019). Klotho induces insulin resistance possibly through interference with GLUT4 translocation and activation of Akt, GSK3β, and PFKfβ3 in 3T3-L1 adipocyte cells. Research in Pharmaceutical Sciences, 14(4), 369. https://doi.org/10.4103/1735-5362.263627

Nabeshima, Y. (2010). [Regulation of calcium homeostasis by α-Klotho and FGF23]. Clinical Calcium, 20(11), 1677–1685. https://pubmed.ncbi.nlm.nih.gov/21037388/

Neitzel, J., Franzmeier, N., Rubinski, A., et al. (2021). KL-VS heterozygosity is associated with lower amyloid-dependent tau accumulation and memory impairment in Alzheimer’s disease. Nature Communications, 12(1). https://doi.org/10.1038/s41467-021-23755-z

Belloy, M. E., Napolioni, V., Han, S. S., et al. (2020). Association ofKlotho-VS Heterozygosity With Risk of Alzheimer Disease in Individuals Who CarryAPOE4. JAMA Neurology, 77(7), 849. https://doi.org/10.1001/jamaneurol.2020.0414

Maurya, R., Bhattacharjee, G., Khambhati, K., et al. (2023, January 1). Chapter Twelve - Amyloid precursor protein in Alzheimer’s disease (I. Mani & V. Singh, Eds.). ScienceDirect; Academic Press. https://www.sciencedirect.com/science/article/abs/pii/S1877117322001351

Zhou, Z., Chan, C. H., Ma, Q., et al. (2011). The roles of amyloid precursor protein (APP) in neurogenesis, implications to pathogenesis and therapy of Alzheimer disease (AD). Cell Adhesion & Migration, 5(4), 280–292. https://doi.org/10.4161/cam.5.4.16986

Cappai, R. (2014). Making sense of the amyloid precursor protein: its tail tells an interesting tale. Journal of Neurochemistry, 130(3), 325–327. https://doi.org/10.1111/jnc.12707

Grimm, M. O. W., Mett, J., Stahlmann, C. P., et al. (2015). APP intracellular domain derived from amyloidogenic β- and γ-secretase cleavage regulates neprilysin expression. Frontiers in Aging Neuroscience, 7, 77. https://doi.org/10.3389/fnagi.2015.00077

Hersh, L., & Rodgers, D. (2008). Neprilysin and Amyloid Beta Peptide Degradation. Current Alzheimer Research, 5(2), 225–231. https://doi.org/10.2174/156720508783954703

Schwarzman, A. L., & Goldgaber, D. (1996). Interaction of transthyretin with amyloid beta-protein: binding and inhibition of amyloid formation. Ciba Foundation Symposium, 199, 146–160; discussion 160-164. https://doi.org/10.1002/9780470514924.ch10

Alemi, M., Gaiteiro, C., Ribeiro, C. A., et al. (2016). Transthyretin participates in beta-amyloid transport from the brain to the liver- involvement of the low-density lipoprotein receptor-related protein 1? Scientific Reports, 6(1). https://doi.org/10.1038/srep20164

Wang, D., Chen, F., & Han, Z et. al (2021, July 19). Relationship Between Amyloid-β Deposition and Blood–Brain Barrier Dysfunction in Alzheimer’s Disease [Review of Relationship Between Amyloid-β Deposition and Blood–Brain Barrier Dysfunction in Alzheimer’s Disease]. Frontiers. https://doi.org/10.3389/fncel.2021.695479

Grimm, M. O. W., Mett, J., Stahlmann, C. P., et al. (2013). Neprilysin and Aβ Clearance: Impact of the APP Intracellular Domain in NEP Regulation and Implications in Alzheimer’s Disease. Frontiers in Aging Neuroscience, 5. https://doi.org/10.3389/fnagi.2013.00098

Zhang, Y., Thompson, R., Zhang, H., et al. (2011). APP processing in Alzheimer’s disease. Molecular Brain, 4(1), 3. https://doi.org/10.1186/1756-6606-4-3

Hernández-Goenaga, J., López-Abán, J., Protasio, A. V., et al. (2019). Peptides Derived of Kunitz-Type Serine Protease Inhibitor as Potential Vaccine Against Experimental Schistosomiasis. Frontiers in Immunology, 10. https://doi.org/10.3389/fimmu.2019.02498

Ho, L., Fukuchi, K., & Younkin, S. G. (1996, November 29). The Alternatively Spliced Kunitz Protease Inhibitor Domain Alters Amyloid b Protein Precursor Processing and Amyloid b Protein Production in Cultured Cells [Review of The Alternatively Spliced Kunitz Protease Inhibitor Domain Alters Amyloid b Protein Precursor Processing and Amyloid b Protein Production in Cultured Cells]. Journal of Biological Chemistry. https://www.jbc.org/article/S0021-9258(19)79152-2/pdf

Iulita, M. F., Garzón Chavez, D., Klitgaard Christensen, M., et al. (2022). Association of Alzheimer Disease With Life Expectancy in People With Down Syndrome. JAMA Network Open, 5(5), e2212910. https://doi.org/10.1001/jamanetworkopen.2022.12910

Alzheimer's Association. (2015). Down Syndrome and Alzheimer’s Disease. Alzheimer’s Disease and Dementia. https://www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia/down-syndrome

Bagaria, J., Bagyinszky, E., & An, S. S. A. (2022). Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene. International Journal of Molecular Sciences, 23(18), 10970. https://doi.org/10.3390/ijms231810970

Kelleher, R. J., & Shen, J. (2017). Presenilin-1 mutations and Alzheimer’s disease. Proceedings of the National Academy of Sciences, 114(4), 629–631. https://doi.org/10.1073/pnas.1619574114

Szaruga, M., Munteanu, B., Lismont, S., et al. (2017). Alzheimer’s-Causing Mutations Shift Aβ Length by Destabilizing γ-Secretase-Aβn Interactions. Cell, 170(3), 443-456.e14. https://doi.org/10.1016/j.cell.2017.07.004

Xiao, X., Liu, H., Liu, X., et al. (2021). APP, PSEN1, and PSEN2 Variants in Alzheimer’s Disease: Systematic Re-evaluation According to ACMG Guidelines. Frontiers in Aging Neuroscience, 13. https://doi.org/10.3389/fnagi.2021.695808

An, S. S., Cai, Y., & Kim, S. (2015). Mutations in Presenilin 2 and Its Implications in Alzheimer’s Disease and Other dementia-associated Disorders. Clinical Interventions in Aging, 10, 1163. https://doi.org/10.2147/cia.s85808

Wolfe, M. S. (2013, January 1). Chapter 66 - Presenilin-2 (N. D. Rawlings & G. Salvesen, Eds.). ScienceDirect; Academic Press. https://doi.org/10.1016/B978-0-12-382219-2.00066-1

Dai, M.-H., Zheng, H., Zeng, L.-D., et al. (2017). The genes associated with early-onset Alzheimer’s disease. Oncotarget, 9(19). https://doi.org/10.18632/oncotarget.23738

National Human Genome Research Institute. (2015). Genome-Wide Association Studies Fact Sheet. Genome.gov. https://www.genome.gov/about-genomics/fact-sheets/Genome-Wide-Association-Studies-Fact-Sheet

Eisenstein, M. (2011). Genetics: Finding risk factors. 475(7355), S20–S22. https://doi.org/10.1038/475s20a

Ge, T., Holmes, A. J., Buckner, R. L., et al. (2017). Heritability analysis with repeat measurements and its application to resting-state functional connectivity. Proceedings of the National Academy of Sciences, 114(21), 5521–5526. https://doi.org/10.1073/pnas.1700765114

Sims, R., Hill, M., & Williams, J. (2020, February 28). The multiplex model of the genetics of Alzheimer’s disease [Review of The multiplex model of the genetics of Alzheimer’s disease]. Nature Neuroscience. https://doi.org/10.1038/s41593-020-0599-5

Alberts, B., Johnson, A., Lewis, J., et al. (2002). Analyzing Protein Structure and Function. Molecular Biology of the Cell. 4th Edition. https://www.ncbi.nlm.nih.gov/books/NBK26820/#:~:text

National Human Genome Research Institute. (2015). Knockout Mice Fact Sheet. Genome.gov. https://www.genome.gov/about-genomics/fact-sheets/Knockout-Mice-Fact-Sheet

Shore, V. G., & Shore, B. (1973). Heterogeneity of human plasma very low density lipoproteins. Separation of species differing in protein components. Biochemistry, 12(3), 502–507. https://doi.org/10.1021/bi00727a022

Smyth, M. S., & Martin, J. H. J. (2000). X Ray Crystallography. Molecular Pathology, 53(1), 8–14. https://doi.org/10.1136/mp.53.1.8

Suppiah, S., Didier, M.-A., & Vinjamuri, S. (2019). The Who, When, Why, and How of PET Amyloid Imaging in Management of Alzheimer’s Disease—Review of Literature and Interesting Images. Diagnostics, 9(2), 65. https://doi.org/10.3390/diagnostics9020065

Pietroboni, A. M., Colombi, A., Carandini, T., et al. (2022). Amyloid PET imaging and dementias: potential applications in detecting and quantifying early white matter damage. Alzheimer’s Research & Therapy, 14(1). https://doi.org/10.1186/s13195-021-00933-1

Creative Commons — Attribution 4.0 International — CC BY 4.0. (2019). Creativecommons.org. http://creativecommons.org/licenses/by/4.0/

Anderson, N. B., Bulatao, R. A., Cohen, B., & National Research Council (US) Panel on Race, E. (2004). Ethnic Differences in Dementia and Alzheimer’s Disease. Www.ncbi.nlm.nih.gov; National Academies Press (US). https://www.ncbi.nlm.nih.gov/books/NBK25535/#:~:text

Mayo Clinic. (2021, June 30). What new Alzheimer’s treatments are on the horizon? Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-treatments/art-20047780

Soeda, Y., & Takashima, A. (2020, December 3). New Insights Into Drug Discovery Targeting Tau Protein [Review of New Insights Into Drug Discovery Targeting Tau Protein]. Frontiers . https://doi.org/10.3389/fnmol.2020.590896

Takeuchi, H., Imamura, K., Ji, B., et al. (2020). Nasal vaccine delivery attenuates brain pathology and cognitive impairment in tauopathy model mice. Npj Vaccines, 5(1), 1–11. https://doi.org/10.1038/s41541-020-0172-y

Miller, J. (2019, September 10). Scientists propose new approach to Alzheimer’s research to address environmental risks. USC News. https://news.usc.edu/160629/alzheimers-environmental-risk-factors-usc-research/

Schultz, S., Larson, J., Oh, J., et al. (2015). Participation in cognitively-stimulating activities is associated with brain structure and cognitive function in preclinical Alzheimer’s disease. Brain Imaging and Behavior, 9(4), 729–736. https://doi.org/10.1007/s11682-014-9329-5

MIND and Mediterranean diets associated with fewer Alzheimer’s plaques and tangles. (n.d.). ScienceDaily. Retrieved June 19, 2023, from http://dx.doi.org/10.1212/WNL.0000000000207176

‌