Scientific Background and Reference Sources
ACMG. (2015). Clinical utility of genetic and genomic services: a position statement of the American College of Medical Genetics and Genomics. Genet Med, 17(6), 505-507. https://doi.org/10.1038/gim.2015.41
ACMG. (2016, September 15). Don’t order APOE genetic testing as a predictive test for Alzheimer disease. https://www.aafp.org/pubs/afp/collections/choosing-wisely/282.html
Athena. (2023a). ADmark® ApoE Genotype Analysis and Interpretation (Symptomatic). https://www.athenadiagnostics.com/view-full-catalog/admark-apoe-genotype-analysis-and-interpretation-symptomatic1
Athena. (2023b). ADmark® Early Onset Alzheimer's Evaluation. https://www.athenadiagnostics.com/view-full-catalog/admark-alzheimers-evaluation1
Cohn-Hokke, P. E., van Swieten, J. C., Pijnenburg, Y. A. L., Tibben, A., Meijers-Heijboer, H., & Kievit, A. (2017). The Effect of Predictive Testing in Adult-Onset Neurodegenerative Diseases on Social and Personal Life. J Genet Couns. https://doi.org/10.1007/s10897-017-0195-3
Cruts, M., Theuns, J., & Van Broeckhoven, C. (2012). Locus-specific mutation databases for neurodegenerative brain diseases. Hum Mutat, 33(9), 1340-1344. https://pubmed.ncbi.nlm.nih.gov/9521418/
Cruts, M., & Van Broeckhoven, C. (1998). Presenilin mutations in Alzheimer's disease. Hum Mutat, 11(3), 183-190. https://doi.org/10.1002/(sici)1098-1004(1998)11:3<183::aid-humu1>3.0.co;2-j
Cummings, J., Apostolova, L., Rabinovici, G. D., Atri, A., Aisen, P., Greenberg, S., Hendrix, S., Selkoe, D., Weiner, M., Petersen, R. C., & Salloway, S. (2023). Lecanemab: Appropriate Use Recommendations. J Prev Alzheimers Dis, 10(3), 362-377. https://doi.org/10.14283/jpad.2023.30
de Calignon, A., Polydoro, M., Suarez-Calvet, M., William, C., Adamowicz, D. H., Kopeikina, K. J., Pitstick, R., Sahara, N., Ashe, K. H., Carlson, G. A., Spires-Jones, T. L., & Hyman, B. T. (2012). Propagation of tau pathology in a model of early Alzheimer's disease. Neuron, 73(4), 685-697. https://doi.org/10.1016/j.neuron.2011.11.033
Dubois, B., Villain, N., Frisoni, G. B., Rabinovici, G. D., Sabbagh, M., Cappa, S., Bejanin, A., Bombois, S., Epelbaum, S., Teichmann, M., Habert, M. O., Nordberg, A., Blennow, K., Galasko, D., Stern, Y., Rowe, C. C., Salloway, S., Schneider, L. S., Cummings, J. L., & Feldman, H. H. (2021). Clinical diagnosis of Alzheimer's disease: recommendations of the International Working Group. Lancet Neurol, 20(6), 484-496. https://doi.org/10.1016/s1474-4422(21)00066-1
FDA. (2017a). DECISION SUMMARY. https://www.accessdata.fda.gov/cdrh_docs/reviews/den160026.pdf
FDA. (2017b). Decision Summary for 23andMe PGS Genetic Health Risk Report. U.S. Food and Drug Administration Retrieved from https://www.accessdata.fda.gov/cdrh_docs/reviews/DEN160026.pdf
Fulgent. (2023). Parkinson-Alzheimer-Dementia NGS Panel. https://www.fulgentgenetics.com/Parkinson-Alzheimer-Dementia
Galluzzi, S., Mega, A., Di Fede, G., Muscio, C., Fascendini, S., Benussi, L., Tagliavini, F., Frisoni, G. B., & Di Maria, E. (2022). Psychological Impact of Predictive Genetic Testing for Inherited Alzheimer Disease and Frontotemporal Dementia: The IT-DIAfN Protocol. Alzheimer Dis Assoc Disord. https://doi.org/10.1097/wad.0000000000000494
Gatz, M., Reynolds, C. A., Fratiglioni, L., Johansson, B., Mortimer, J. A., Berg, S., Fiske, A., & Pedersen, N. L. (2006). Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry, 63(2), 168-174. https://doi.org/10.1001/archpsyc.63.2.168
Giau, V. V., Bagyinszky, E., Yang, Y. S., Youn, Y. C., An, S. S. A., & Kim, S. Y. (2019). Genetic analyses of early-onset Alzheimer's disease using next generation sequencing. Scientific reports, 9(1), 8368-8368. https://doi.org/10.1038/s41598-019-44848-2
Goate, A., Chartier-Harlin, M. C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., & et al. (1991). Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature, 349(6311), 704-706. https://doi.org/10.1038/349704a0
Goldman, J. S., Hahn, S. E., Catania, J. W., LaRusse-Eckert, S., Butson, M. B., Rumbaugh, M., Strecker, M. N., Roberts, J. S., Burke, W., Mayeux, R., & Bird, T. (2011). Genetic counseling and testing for Alzheimer disease: Joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med, 13(6), 597-605. https://doi.org/10.1097/GIM.0b013e31821d69b8
Goldman, J. S., Hahn, S. E., Catania, J. W., LaRusse-Eckert, S., Butson, M. B., Rumbaugh, M., Strecker, M. N., Roberts, J. S., Burke, W., Mayeux, R., & Bird, T. (2019). ADDENDUM: Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med, 21(10), 2404. https://doi.org/10.1038/s41436-019-0559-1
Hort, J., O'Brien, J. T., Gainotti, G., Pirttila, T., Popescu, B. O., Rektorova, I., Sorbi, S., & Scheltens, P. (2010). EFNS guidelines for the diagnosis and management of Alzheimer's disease. Eur J Neurol, 17(10), 1236-1248. https://doi.org/10.1111/j.1468-1331.2010.03040.x
Invitae. (2023). Invitae Hereditary Alzheimer's Disease Panel. https://www.invitae.com/en/physician/tests/03504/
Jack, C. R., Jr., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., Liu, E., Molinuevo, J. L., Montine, T., Phelps, C., Rankin, K. P., Rowe, C. C., Scheltens, P., Siemers, E., Snyder, H. M., . . . Silverberg, N. (2018). NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 14(4), 535-562. https://doi.org/10.1016/j.jalz.2018.02.018
Janssen, J. C., Beck, J. A., Campbell, T. A., Dickinson, A., Fox, N. C., Harvey, R. J., Houlden, H., Rossor, M. N., & Collinge, J. (2003). Early onset familial Alzheimer's disease: Mutation frequency in 31 families. Neurology, 60(2), 235-239. http://n.neurology.org/content/60/2/235.long
Karch, C. M., Cruchaga, C., & Goate, A. M. (2014). Alzheimer's disease genetics: from the bench to the clinic. Neuron, 83(1), 11-26. https://doi.org/10.1016/j.neuron.2014.05.041
Keene, C. D., Montine, Thomas, Kuller, Lewis. (2023, January 19). Epidemiology, pathology, and pathogenesis of Alzheimer disease. https://www.uptodate.com/contents/epidemiology-pathology-and-pathogenesis-of-alzheimer-disease
Knopman, D. S., DeKosky, S. T., Cummings, J. L., Chui, H., Corey-Bloom, J., Relkin, N., Small, G. W., Miller, B., & Stevens, J. C. (2001). Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 56(9), 1143-1153. https://doi.org/10.1212/wnl.56.9.1143
Kumar, A., Tsao, Jack. (2018). Alzheimer Disease. https://www.ncbi.nlm.nih.gov/books/NBK499922/
Lanoiselee, H. M., Nicolas, G., Wallon, D., Rovelet-Lecrux, A., Lacour, M., Rousseau, S., Richard, A. C., Pasquier, F., Rollin-Sillaire, A., Martinaud, O., Quillard-Muraine, M., de la Sayette, V., Boutoleau-Bretonniere, C., Etcharry-Bouyx, F., Chauvire, V., Sarazin, M., le Ber, I., Epelbaum, S., Jonveaux, T., . . . Campion, D. (2017). APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases. PLoS Med, 14(3), e1002270. https://doi.org/10.1371/journal.pmed.1002270
Largent, E. A., Stites, S. D., Harkins, K., & Karlawish, J. (2021). 'That would be dreadful': The ethical, legal, and social challenges of sharing your Alzheimer's disease biomarker and genetic testing results with others. J Law Biosci, 8(1), lsab004. https://doi.org/10.1093/jlb/lsab004
Mehdizadeh, E., Khalaj-Kondori, M., Shaghaghi-Tarakdari, Z., Sadigh-Eteghad, S., Talebi, M., & Andalib, S. (2019). Association of MS4A6A, CD33, and TREM2 gene polymorphisms with the late-onset Alzheimer's disease. Bioimpacts, 9(4), 219-225. https://doi.org/10.15171/bi.2019.27
Naj, A. C., Jun, G., Reitz, C., Kunkle, B. W., Perry, W., Park, Y. S., Beecham, G. W., Rajbhandary, R. A., Hamilton-Nelson, K. L., Wang, L. S., Kauwe, J. S., Huentelman, M. J., Myers, A. J., Bird, T. D., Boeve, B. F., Baldwin, C. T., Jarvik, G. P., Crane, P. K., Rogaeva, E., . . . Yu, L. (2014). Effects of multiple genetic loci on age at onset in late-onset Alzheimer disease: a genome-wide association study. JAMA Neurol, 71(11), 1394-1404. https://doi.org/10.1001/jamaneurol.2014.1491
NIH. (2022). Alzheimer's Disease Diagnostic Guidelines. https://www.nia.nih.gov/health/alzheimers-disease-diagnostic-guidelines
Owens, D. K., Davidson, K. W., Krist, A. H., Barry, M. J., Cabana, M., Caughey, A. B., Doubeni, C. A., Epling, J. W., Jr., Kubik, M., Landefeld, C. S., Mangione, C. M., Pbert, L., Silverstein, M., Simon, M. A., Tseng, C. W., & Wong, J. B. (2020). Screening for Cognitive Impairment in Older Adults: US Preventive Services Task Force Recommendation Statement. Jama, 323(8), 757-763. https://doi.org/10.1001/jama.2020.0435
Pavarini, G., Hamdi, L., Lorimer, J., & Singh, I. (2021). Young people's moral attitudes and motivations towards direct-to-consumer genetic testing for inherited risk of Alzheimer disease. Eur J Med Genet, 64(6), 104180. https://doi.org/10.1016/j.ejmg.2021.104180
Pena-Bautista, C., Roca, M., Lopez-Cuevas, R., Baquero, M., Vento, M., & Chafer-Pericas, C. (2020). Metabolomics study to identify plasma biomarkers in alzheimer disease: ApoE genotype effect. J Pharm Biomed Anal, 180, 113088. https://doi.org/10.1016/j.jpba.2019.113088
Prince, M. (2016). World Alzheimer Report 2015. A. s. D. International. https://www.alzint.org/u/WorldAlzheimerReport2015.pdf
Qin, Q., Yin, Y., Wang, Y., Lu, Y., Tang, Y., & Jia, J. (2020). Gene mutations associated with early onset familial Alzheimer's disease in China: An overview and current status. Molecular genetics & genomic medicine, 8(10), e1443-e1443. https://doi.org/10.1002/mgg3.1443
Rajabli, F., Feliciano, B. E., Celis, K., Hamilton-Nelson, K. L., Whitehead, P. L., Adams, L. D., Bussies, P. L., Manrique, C. P., Rodriguez, A., Rodriguez, V., Starks, T., Byfield, G. E., Sierra Lopez, C. B., McCauley, J. L., Acosta, H., Chinea, A., Kunkle, B. W., Reitz, C., Farrer, L. A., . . . Pericak-Vance, M. A. (2018). Ancestral origin of ApoE epsilon4 Alzheimer disease risk in Puerto Rican and African American populations. PLoS Genet, 14(12), e1007791. https://doi.org/10.1371/journal.pgen.1007791
Roche. (2024). Roche's Elecsys Amyloid Plasma Panel Granted FDA Breakthrough Device Designation to Enable a Timely Diagnosis of Alzheimer’s Disease. https://diagnostics.roche.com/us/en/news-listing/2022/elecsys-amyloid-plasma-panel-fda-breakthrough-device-designation-alzheimers.html
Ryman, D. C., Acosta-Baena, N., Aisen, P. S., Bird, T., Danek, A., Fox, N. C., Goate, A., Frommelt, P., Ghetti, B., Langbaum, J. B., Lopera, F., Martins, R., Masters, C. L., Mayeux, R. P., McDade, E., Moreno, S., Reiman, E. M., Ringman, J. M., Salloway, S., . . . Bateman, R. J. (2014). Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology, 83(3), 253-260. https://doi.org/10.1212/wnl.0000000000000596
Schneider, L. S., Mangialasche, F., Andreasen, N., Feldman, H., Giacobini, E., Jones, R., Mantua, V., Mecocci, P., Pani, L., Winblad, B., & Kivipelto, M. (2014). Clinical trials and late-stage drug development for Alzheimer's disease: an appraisal from 1984 to 2014. J Intern Med, 275(3), 251-283. https://doi.org/10.1111/joim.12191
Shea, Y. F., Chu, L. W., Chan, A. O., Ha, J., Li, Y., & Song, Y. Q. (2016). A systematic review of familial Alzheimer's disease: Differences in presentation of clinical features among three mutated genes and potential ethnic differences. J Formos Med Assoc, 115(2), 67-75. https://doi.org/10.1016/j.jfma.2015.08.004
Sherrington, R., Froelich, S., Sorbi, S., Campion, D., Chi, H., Rogaeva, E. A., Levesque, G., Rogaev, E. I., Lin, C., Liang, Y., Ikeda, M., Mar, L., Brice, A., Agid, Y., Percy, M. E., Clerget-Darpoux, F., Piacentini, S., Marcon, G., Nacmias, B., . . . St George-Hyslop, P. H. (1996). Alzheimer's disease associated with mutations in presenilin 2 is rare and variably penetrant. Hum Mol Genet, 5(7), 985-988.
Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., Tsuda, T., Mar, L., Foncin, J. F., Bruni, A. C., Montesi, M. P., Sorbi, S., Rainero, I., Pinessi, L., Nee, L., . . . St George-Hyslop, P. H. (1995). Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature, 375(6534), 754-760. https://doi.org/10.1038/375754a0
Sherva, R., & Kowall, N. W. (2023, July 23). Genetics of Alzheimer disease. https://www.uptodate.com/contents/genetics-of-alzheimer-disease
Sorbi, S., Hort, J., Erkinjuntti, T., Fladby, T., Gainotti, G., Gurvit, H., Nacmias, B., Pasquier, F., Popescu, B. O., Rektorova, I., Religa, D., Rusina, R., Rossor, M., Schmidt, R., Stefanova, E., Warren, J. D., & Scheltens, P. (2012). EFNS-ENS Guidelines on the diagnosis and management of disorders associated with dementia. Eur J Neurol, 19(9), 1159-1179. https://doi.org/10.1111/j.1468-1331.2012.03784.x
St George-Hyslop, P. H., Tanzi, R. E., Polinsky, R. J., Haines, J. L., Nee, L., Watkins, P. C., Myers, R. H., Feldman, R. G., Pollen, D., Drachman, D., & et al. (1987). The genetic defect causing familial Alzheimer's disease maps on chromosome 21. Science, 235(4791), 885-890.
Stevenson-Hoare, J., Heslegrave, A., Leonenko, G., Fathalla, D., Bellou, E., Luckcuck, L., Marshall, R., Sims, R., Morgan, B. P., Hardy, J., de Strooper, B., Williams, J., Zetterberg, H., & Escott-Price, V. (2023). Plasma biomarkers and genetics in the diagnosis and prediction of Alzheimer's disease. Brain, 146(2), 690-699. https://doi.org/10.1093/brain/awac128
Van Broeckhoven, C., Backhovens, H., Cruts, M., De Winter, G., Bruyland, M., Cras, P., & Martin, J. J. (1992). Mapping of a gene predisposing to early-onset Alzheimer's disease to chromosome 14q24.3. Nat Genet, 2(4), 335-339. https://doi.org/10.1038/ng1292-335
Van Cauwenberghe, C., Van Broeckhoven, C., & Sleegers, K. (2016). The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genet Med, 18(5), 421-430. https://doi.org/10.1038/gim.2015.117
Weintraub, S., Teylan, M., Rader, B., Chan, K. C. G., Bollenbeck, M., Kukull, W. A., Coventry, C., Rogalski, E., Bigio, E., & Mesulam, M. M. (2020). APOE is a correlate of phenotypic heterogeneity in Alzheimer disease in a national cohort. Neurology, 94(6), e607-e612. https://doi.org/10.1212/wnl.0000000000008666
WHO. (2023). Dementia. https://www.who.int/news-room/fact-sheets/detail/dementia
Wong, T. H., Seelaar, H., Melhem, S., Rozemuller, A. J. M., & van Swieten, J. C. (2020). Genetic screening in early-onset Alzheimer's disease identified three novel presenilin mutations. Neurobiol Aging, 86, 201.e209-201.e214. https://doi.org/10.1016/j.neurobiolaging.2019.01.015
Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C. C., & Bu, G. (2019). Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. Nat Rev Neurol, 15(9), 501-518. https://doi.org/10.1038/s41582-019-0228-7
Zhang, X., Zhu, C., Beecham, G., Vardarajan, B. N., Ma, Y., Lancour, D., Farrell, J. J., Chung, J., Mayeux, R., Haines, J. L., Schellenberg, G. D., Pericak-Vance, M. A., Lunetta, K. L., & Farrer, L. A. (2019). A rare missense variant of CASP7 is associated with familial late-onset Alzheimer's disease. Alzheimers Dement, 15(3), 441-452. https://doi.org/10.1016/j.jalz.2018.10.005
Medical Director Review- 07/2023
Medical Director Review- 10/2024