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Frontiers in Dementia ·

Volume 5 - 2026 | https://doi.org/10.3389/frdem.2026.1808512

Now is the time: the need to update guidance to expand access to APOE genetic testing

  • Wendy R. Uhlmann1*corresponding author
  • Amanda K. Chan2
  • Jill S. Goldman2
  1. 1Division of Genetic Medicine, Department of Internal Medicine and Department of Human Genetics, University of Michigan, Ann Arbor, MI, United States
  2. 2Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States
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Abstract

Interest in APOE testing has increased due to an aging population, direct-to-consumer testing options, media coverage and FDA approval of anti-amyloid therapies. Previous Alzheimer’s disease (AD) guidelines cautioned against APOE testing in asymptomatic individuals. However, updated guidance is warranted due to the changing landscape and research demonstrating low adverse psychological outcomes of APOE testing. With testing for APOE now recommended prior to anti-amyloid therapies, more symptomatic individuals will be identified as having the higher risk ε4 variant. The children and siblings of the symptomatic individuals who test positive will have at least a 50% risk of also having an ε4 and may subsequently seek testing. Since testing for APOE is generally not clinically available to asymptomatic individuals, they may pursue direct-to-consumer genetic testing and, therefore, be tested without a clinician’s involvement or counseling. Given limitations and caveats of APOE testing, it is important that patients have access to education, counseling and testing in labs certified for clinical testing. Pre- and post-test education and counseling content for APOE testing, including risk figures, are provided in this Perspective. Both Alzheimer’s disease and cardiovascular disease risks associated with APOE should be addressed for all individuals undergoing testing. Given that it has been over a decade since APOE guidance was issued, the time has come for the medical community to discuss the changing landscape, expand APOE genetic testing access to individuals at higher risk, and update guidelines.

Keywords

1. Introduction

Fear of developing Alzheimer’s disease (AD) is a common aging concern, and genetic testing is frequently requested. More than 80 AD susceptibility genes have been identified with the Apolipoprotein E gene (APOE) being the first and conferring the strongest impact on risk for late-onset disease (>65 years old) (Serrano-Pozo et al., 2021). While the APOE ε4 variant is the most significant genetic AD risk factor, clinical guidelines have historically discouraged both diagnostic and predictive APOE testing because an ε4 variant is neither necessary nor sufficient for developing AD (American College of Medical Genetics/American Society of Human Genetics Working Group, 1995; Relkin et al., 1996; Waldemar et al., 2007; Goldman et al., 2011). However, the landscape around APOE testing is changing because: (1) there are demographic changes with a larger aging population at risk for AD (Alzheimer’s Association, 2025), (2) APOE testing is now recommended before utilizing anti-amyloid therapies (e.g., Lecanemab) given increased risk for ARIA (amyloid-related imaging abnormalities) associated with an ε4 variant (van Dyck et al., 2023), (3) APOE testing is recommended to assess cardiovascular disease (CVD) risk for individuals with possible dyslipidemia (Ison et al., 2025), (4) increased APOE testing of individuals who are symptomatic for AD and/or individuals with possible dyslipidemia will reveal the increased risk for being an APOE ε4 carrier to their asymptomatic children and siblings who may subsequently seek testing, (5) APOE genotype is frequently part of eligibility criteria for AD research and clinical trials (Langbaum et al., 2019), (6) there is a growing general population interest in learning AD risk due to media coverage (Breznican, 2022), and (7) testing can be found on the internet and accessed through direct-to-consumer (DTC) companies without clinician involvement. Guidelines for AD genetic testing were last issued in 2011 (Goldman et al., 2011). Given the changing landscape around APOE testing, this Perspective advocates for increasing access to clinical APOE testing, discusses key information to convey to patients, and recommends updating decades-old professional guidelines.

2. Discussion

APOE -associated risk

The APOE ε 4 allele is seen in approximately 60% of individuals with AD and 20–25% in the general population (Van Cauwenberghe et al., 2016). Based on longitudinal studies, the risk of clinical symptoms of mild cognitive impairment (MCI) and dementia by age 85 years is 10 to 15% without an APOE ε 4, 20 to 25% with one ε4 allele, and 30 to 55% with two copies of ε4 though these estimates likely differ by ancestry (Qian et al., 2017; Belloy et al., 2023). Homozygosity for APOE ε4 is seen in approximately 2% of the general population and up to 15% of individuals with AD (Corder et al., 1993; Belloy et al., 2019). Of note, a 2024 study by Fortea et al. (2024) suggested that APOE ε4 homozygosity be considered a genetic form of AD, resulting in wide media attention and increased general population interest in APOE testing (Belluck, 2024; Neergaard, 2024). However, the Fortea et al. (2024) study was limited by assessment of only biological penetrance rather than clinical penetrance of symptoms and was not based on longitudinal studies that considered ethnicity and race (Reiman et al., 2025). APOE remains an AD susceptibility risk gene and is not deterministic unlike the highly penetrant PSEN1, PSEN2 and APP genes that cause early-onset autosomal dominant AD.

Clinical practice update needed for APOE testing

APOE genetic testing is not currently recommended for all symptomatic individuals since having an ε4 is neither necessary nor sufficient for AD. However, clinical APOE testing is recommended for symptomatic patients considering anti-amyloid therapies given increased ARIA risk if found to have an APOE ε4 variant (Cummings et al., 2022, 2023). An increase in APOE testing means that more symptomatic individuals will be identified as ε4 carriers. Children and siblings of ε4 carriers have at least a 50% risk of also having an ε4 (Table 1) and may subsequently seek testing. In addition, some individuals with actual or perceived cognitive symptoms may request APOE testing to have another data point about a possible AD diagnosis.

For any individual considering APOE testing, the education and counseling content covered in this Perspective and in Table 1 are key to understanding its limitations and nuances and should be conveyed by the healthcare provider or through referral to a genetic counselor. After provision of this information, if a symptomatic patient or an asymptomatic patient with a first-degree affected relative and/or known APOE ε4 in the family subsequently wishes to proceed with APOE testing, then we advocate this should be a clinical option and incorporated into guidelines. It is preferable for individuals to have pre- and post-test counseling with Table 1 points covered rather than proceeding with direct-to-consumer (DTC) genetic testing without a clinician’s involvement. Furthermore, DTC testing raises the concern of a commercial entity having private patient healthcare information and the potential for data-sharing.

Changing landscape: pros and cons of asymptomatic APOE testing

Though historically, APOE testing has not been recommended for asymptomatic individuals (American College of Medical Genetics/American Society of Human Genetics Working Group, 1995; Relkin et al., 1996; Waldemar et al., 2007; Goldman et al., 2011), we believe it is time to reconsider for individuals who have a first-degree affected relative and/or known APOE ε4 in the family. If a first-degree relative is affected, the risk for AD is increased to 20–25%, or higher if multiple family members have late-onset AD (Bird, 2008; Cannon-Albright et al., 2019). The increased AD risks due to having an APOE ε4 are noted above. While concern is understandable, an affected second-degree relative (e.g., grandparent) generally would not be an indication for APOE testing. A grandchild’s risk is not significantly increased (though risk figures are not readily available) and would be dependent on whether their parent develops AD.

While positive APOE ε4 carrier status currently has no impact on medical care for an asymptomatic individual, studies have shown that it can hold personal utility and there is high interest about learning AD risk (Marshe et al., 2019; Ryan et al., 2021). Individuals have made lifestyle changes (i.e., exercise, diet) and engaged in future planning after learning about their APOE ε4 carrier status (Chao et al., 2008; Largent et al., 2021). Knowledge of positive APOE ε4 carrier status may also encourage engagement in AD research studies or clinical trials focused on prevention (Iacono, 2025). Furthermore, though APOE is an AD risk factor and is not ready for utilization in population-level screening, the field is shifting to earlier prediction and potentially prevention of AD; APOE genotyping is one component that can be used to work toward achieving this goal.

Research mostly on individuals with a family history of AD has shown that APOE testing in asymptomatic individuals is relatively safe with few adverse psychological outcomes when accompanied by pre- and post-test counseling (Cassidy et al., 2008; Green et al., 2009; Largent et al., 2021; Alber et al., 2022; Langbaum et al., 2025). It has also been shown to be safe when performed by condensed counseling approaches (Roberts et al., 2012; Green et al., 2015) and by telephone counseling (Christensen et al., 2018). Furthermore, APOE disclosure for individuals with mild cognitive impairment (MCI) similarly did not show significant increases in anxiety and depression (Christensen et al., 2020) when accompanied by pre- and post-test counseling. In 2017, the FDA considered APOE testing safe enough to issue approval for the company 23andMe to offer this testing DTC (Maxmen, 2017).

Another reason to reconsider offering APOE testing is the association between APOE and cardiovascular risk (Table 1). Inclusion of APOE in routine CVD screening for dyslipidemia is recommended (Sturm et al., 2018) and the importance of counseling is noted if ε4 status is reported or revealed (Ison et al., 2025). We recommend clinicians counsel on both cardiovascular and AD implications when ordering APOE testing in any setting. Studies on learning about APOE- associated risk for both AD and CVD are limited but a randomized trial suggested that it is psychologically safe to disclose these risks with pre- and post-test counseling, and led to some study participants making health behavior changes when provided with risk modification information for CVD (Christensen et al., 2016). Additionally, research indicates that having an APOE ε4 may reduce response to statins and needs to be considered when prescribing statins (Asiimwe et al., 2026).

A potential concern for asymptomatic APOE disclosure is whether individuals can comprehend results or will misinterpret the significance of APOE being a risk factor and not a deterministic gene. A 2021 study demonstrated that cognitively unimpaired APOE ε4 carriers who received pre- and post- test counseling understood the implications of their results (Largent et al., 2021). However, APOE status may influence risk perception with Langbaum et al. (2025) showing that APOE ε4 homozygotes possessed a higher perceived AD risk from their pre-test baseline compared to APOE ε4 heterozygotes and non-carriers (Langbaum et al., 2025). In addition to risk perception, knowledge of one’s increased AD risk due to APOE ε4 may impact current cognitive functioning in asymptomatic individuals (Lineweaver et al., 2014) and self-perceptions and attitudes about one’s memory (Largent et al., 2021; Iacono, 2025).

Other commonly cited harms of APOE ε4 disclosure to asymptomatic individuals include the immediate psychological reactions and potential long-term psychological burden of having an increased risk of AD. These harms can be exacerbated by the method of result disclosure. Many people, including well-known celebrities such as actor Chris Hemsworth, have sought DTC APOE testing (Breznican, 2022; Hamilton, 2025). This generally has been done in the absence of any counseling and some individuals report adverse psychological reactions (depression, anxiety) when learning their results without clinician involvement (Messner, 2011; Koeller et al., 2017; Zallen, 2018; Steenhuysen, 2023; Schonbek, 2024). The timing of learning about APOE results is also a consideration and Iacono (2025) discusses pros and cons of disclosure in early adulthood. Ethical questions also exist about whether knowing one’s APOE status could lead to stigma and discrimination for certain types of insurance and in the workplace (Iacono, 2025).

Pre- and post-test APOE counseling

Pre- and post-test counseling should include information on APOE ’s association with AD and CVD risk, how APOE is inherited, and the personal and familial implications of knowing one’s APOE status (Table 1). Common clinical scenarios of APOE testing, topics to address (including suggested wording for risk communication, ascertaining risk perceptions) and recommended next steps are presented in a paper by Stites et al. (2022) and APOE counseling considerations, approaches and tips are presented in Zampatti et al. (2025).

We recommend pre- and post-test counseling for higher risk asymptomatic individuals interested in APOE testing. Counseling can be facilitated by genetic counselors, specialists, or primary care providers (Stites et al., 2022). Symptomatic individuals may also benefit from meeting with a genetic counselor if they want further discussion or need additional education for decision-making (Rumbaugh and Chan, 2025; Zampatti et al., 2025).

For all patients, ascertaining family history is important for determining risk, appropriate genetic testing, and familial implications. This includes obtaining age of onset/age at diagnosis, the presenting symptoms and any comorbidities to rule out other neurological/genetic conditions. For deceased individuals, it is important to determine if an autopsy was performed to confirm the type of dementia. While the focus for symptomatic individuals may be largely on the APOE gene for treatment decisions, a multigene panel of autosomal dominant dementia genes may be indicated if the patient has early-onset symptoms and/or a positive family history of early-onset AD/dementia.

APOE genetic counseling for asymptomatic individuals

In addition to the above pre- and post-test counseling and Table 1 information, there are specific considerations for asymptomatic individuals. Family history should be reviewed to evaluate risk of AD versus a different dementia and to assess the mode of inheritance in the family (Goldman et al., 2011; Pagano et al., 2024). It is not unusual to have multiple affected relatives since up to 25% of all AD is familial of which 95% is late-onset (Bird, 2018). The family history assessment could significantly impact the genetic testing that is considered; the at-risk individual may ask incorrectly for APOE testing instead of testing for autosomal dominant dementia genes. Other risk factors should also be ascertained (e.g., alcohol, lack of sleep, heart disease) and patients should be encouraged to discuss lifestyle modifications with their primary healthcare provider to reduce AD risk.

Clinicians should stress that APOE ε4 is one of many genetic and environmental factors contributing to AD risk and that available risk figures are based primarily on individuals of European ancestry; further research is needed to clarify lifetime risk estimates for other ethnicities. Asymptomatic individuals should understand that AD is not inevitable if an APOE ε4 variant is identified. Just 60% of individuals with AD have an APOE ε4 variant (Van Cauwenberghe et al., 2016). Furthermore, if an affected parent’s ε4 is not inherited, AD risk is partially reduced but not eliminated.

Counseling should also explore the potential psychological impact of knowledge of one’s APOE status. Though most individuals find the information helpful and cope well with their results, as previously noted, some may have adverse psychological reactions, especially when pre-test genetic counseling was not received. Referral to a mental health professional may be advisable.

There are insurance considerations that need to be discussed during counseling asymptomatic individuals. Health insurance may not cover the genetic testing costs if asymptomatic. Other types of insurance can be impacted for asymptomatic individuals and genetic non-discrimination laws differ by country (Prince, 2019; Joly et al., 2020). In the United States, the Genetic Information Non-Discrimination Act (GINA) protects against discrimination in employment and for health insurance with some caveats but does not cover life, disability or long-term care insurance (Genetic Discrimination-National Human Genome Research Institute, 2025). Helpful information on GINA is available at https://ginahelp.org/

Finally, asymptomatic individuals should be aware that testing of other biomarkers in blood, cerebrospinal fluid, and brain amyloid PET scans provide stronger AD prognostic and diagnostic evidence (Bouwman et al., 2022; Chapleau et al., 2022; Mielke and Fowler, 2024). In fact, usage of biomarker-based testing is expanding and the FDA recently approved the first blood-based AD biomarker test (Rubin, 2025). However, caution needs to be given to the potential for over-diagnosis solely based on a single biomarker or genetic test due to limitations of test sensitivity and specificity (Alzforum, 2025). It is important in developing guidance to look beyond just APOE testing to the future usage of these biomarker-based tests in asymptomatic individuals interested in ascertaining AD risk.

Challenges of implementing clinical APOE testing for asymptomatic individuals

There are practice implications for expanding access to clinical APOE testing given the potential high interest. Clinicians in different clinical specialties and work settings can use the information in this Perspective to inform patients, facilitate decision-making, and streamline the communication of information. While neurologists, cardiologists, or primary care providers can generally convey the risk information discussed in this Perspective and order testing, genetic counselors involvement is recommended in certain clinical situations requiring extended discussion (e.g., autosomal dominant family history), especially with asymptomatic patients (Ritchie et al., 2024). Given patient volumes, the use of digital tools (e.g., chatbots) to assist with APOE education may be helpful and allow clinicians time to focus on risk assessment, decision-making, and interpretation of test results (Shickh et al., 2021; Erickson et al., 2025; Wood et al., 2025).

3. Conclusions

APOE testing is an important component of risk assessment for AD and can yield results that are useful for both symptomatic and asymptomatic individuals. For symptomatic individuals, results can impact clinical care and provide risk information for family members. For asymptomatic individuals, there is the opportunity to clarify one’s AD risk, information which can be used to potentially make lifestyle modifications and inform future planning. Therefore, while APOE testing is neither diagnostic nor predictive for AD, it can hold value in patient care and personal utility for decision-making and life planning.

As experienced neurogenetic counselors, we frequently receive requests for APOE testing from asymptomatic patients and believe individuals with a first-degree affected relative and/or known APOE ε4 in the family should have the option of clinical testing with genetic counseling rather than DTC testing without it. However, wider access should not be implemented until guidance is provided by the neurology and genetics communities. The AD field is expanding beyond APOE to the use of other biomarkers. An update in guidance is needed given the increasing use of APOE testing in treatment decisions and would be particularly timely since AD polygenic risk scores (PRS) and testing for other AD biomarkers are anticipated to be introduced for asymptomatic individuals (Baker and Escott-Price, 2020; Grill, 2025). With multiple landscape changes and the shift toward earlier identification of individuals at-risk for AD, we think it is time as a medical community to discuss expanding clinical APOE genetic testing access and update guidelines.

Statements

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

The author(s) declared that financial support was not received for this work and/or its publication.

Data availability

The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding author.

Author contributions

WU: Conceptualization, Writing – original draft, Writing – review & editing. AC: Conceptualization, Writing – original draft, Writing – review & editing. JG: Conceptualization, Writing – original draft, Writing – review & editing.

References

  1. Alber J., Popescu D., Thompson L. I., Tonini G.-M., Arthur E., Oh H.. (2022). Safety and tolerability of APOE genotyping and disclosure in cognitively normal volunteers from the Butler Alzheimer’s prevention registry. J. Geriatr. Psychiatry Neurol. 35, 293 – 301. doi:, doi:10.1177/0891988721993575
  2. Alzforum (2025). Trouble with Fujirebio’s FDA-cleared blood test? Or a lousy lot? Available online at: (accessed December 10, 2025).
  3. Alzheimer’s Association (2025). 2025 Alzheimer’s disease facts and figures. Alzheimers Dement. 21: e70235. doi: doi:10.1002/alz.70235
  4. American College of Medical Genetics/American Society of Human Genetics Working Group (1995). Statement on use of apolipoprotein E testing for Alzheimer disease. American College of Medical Genetics/American Society of Human Genetics working group on ApoE and Alzheimer disease. JAMA 274, 1627 – 1629. doi: doi:10.1001/jama.1995.03530200063039
  5. Asiimwe I. G., Gebru T., Jorgensen A. L., Pirmohamed M. Multimorbidity Mechanism and Therapeutics Research Collaborative (2026). APOE genotype and the effect of statins on lipid outcomes: a meta-analysis. Br. J. Clin. Pharmacol. 92, 1268 – 1286. doi: doi:10.1002/bcp.70493
  6. Baker E., Escott-Price V. (2020). Polygenic risk scores in Alzheimer’s disease: current applications and future directions. Front. Digit. Health 2: 14. doi:, doi:10.3389/fdgth.2020.00014
  7. Belloy M. E., Andrews S. J., Le Guen Y., Cuccaro M., Farrer L. A., Napolioni V.. (2023). APOE genotype and Alzheimer disease risk across age, sex, and population ancestry. JAMA Neurol. 80, 1284 – 1294. doi:, doi:10.1001/jamaneurol.2023.3599
  8. Belloy M. E., Napolioni V., Greicius M. D. (2019). A quarter century of APOE and Alzheimer’s disease: Progress to date and the path forward. Neuron 101, 820 – 838. doi:, doi:10.1016/j.neuron.2019.01.056
  9. Belluck P. (2024). Study suggests genetics as a cause, not just a risk, for some Alzheimer’s. The New York Times. Available online at: (accessed December 10, 2025).
  10. Bird T. D. (2008). Genetic aspects of Alzheimer disease. Genet. Med. 10, 231 – 239. doi:, doi:10.1097/GIM.0b013e31816b64dc
  11. Bird T. D. (2018). “ Alzheimer Disease Overview,” in GeneReviews®, eds. Adam M. P., Bick S., Mirzaa G. M., Pagon R. A., Wallace S. E., Amemiya A. (Seattle (WA): University of Washington, Seattle).
  12. Bouwman F. H., Frisoni G. B., Johnson S. C., Chen X., Engelborghs S., Ikeuchi T.. (2022). Clinical application of CSF biomarkers for Alzheimer’s disease: from rationale to ratios. Alzheimers Dement. 14: e12314. doi:, doi:10.1002/dad2.12314
  13. Breznican A. (2022). Chris Hemsworth changed his life after an ominous health warning. Vanity Fair. Available online at: (accessed December 10, 2025).
  14. Cannon-Albright L., Foster N., Schliep K., Farnham J., Teerlink C., Kaddas H.. (2019). Relative risk for Alzheimer disease based on complete family history. Neurology 92, e1745 – e1753. doi:, doi:10.1212/WNL.0000000000007231
  15. Cassidy M. R., Roberts J. S., Bird T. D., Steinbart E. J., Cupples L. A., Chen C. A.. (2008). Comparing test-specific distress of susceptibility versus deterministic genetic testing for Alzheimer’s disease. Alzheimers Dement. 4, 406 – 413. doi:, doi:10.1016/j.jalz.2008.04.007
  16. Chao S., Roberts J. S., Marteau T. M., Silliman R., Cupples L. A., Green R. C. (2008). Health behavior changes after genetic risk assessment for Alzheimer disease: the REVEAL study. Alzheimer Dis. Assoc. Disord. 22, 94 – 97. doi:, doi:10.1097/WAD.0b013e31815a9dcc
  17. Chapleau M., Iaccarino L., Soleimani-Meigooni D., Rabinovici G. D. (2022). The role of amyloid PET in imaging neurodegenerative disorders: a review. J. Nucl. Med. 63, 13S – 19S. doi:, doi:10.2967/jnumed.121.263195
  18. Christensen K. D., Karlawish J., Roberts J. S., Uhlmann W. R., Harkins K., Wood E. M.. (2020). Disclosing genetic risk for Alzheimer’s dementia to individuals with mild cognitive impairment. Alzheimers Dement 6: e12002. doi:, doi:10.1002/trc2.12002
  19. Christensen K. D., Roberts J. S., Whitehouse P. J., Royal C. D. M., Obisesan T. O., Cupples L. A.. (2016). Disclosing pleiotropic effects during genetic risk assessment for Alzheimer disease: a randomized trial. Ann. Intern. Med. 164, 155 – 163. doi:, doi:10.7326/M15-0187
  20. Christensen K. D., Uhlmann W. R., Roberts J. S., Linnenbringer E., Whitehouse P. J., Royal C. D. M.. (2018). A randomized controlled trial of disclosing genetic risk information for Alzheimer disease via telephone. Genet. Med. 20, 132 – 141. doi:, doi:10.1038/gim.2017.103
  21. Corder E. H., Saunders A. M., Strittmatter W. J., Schmechel D. E., Gaskell P. C., Small G. W.. (1993). Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261, 921 – 923. doi:, doi:10.1126/science.8346443
  22. Cummings J., Apostolova L., Rabinovici G. D., Atri A., Aisen P., Greenberg S.. (2023). Lecanemab: Appropriate Use Recommendations. J. Prev Alzheimers Dis. 10, 362 – 377. doi:, doi:10.14283/jpad.2023.30
  23. Cummings J., Rabinovici G. D., Atri A., Aisen P., Apostolova L. G., Hendrix S.. (2022). Aducanumab: appropriate use recommendations update. J. Prev Alzheimers Dis. 9, 221 – 230. doi:, doi:10.14283/jpad.2022.34
  24. Erickson C. M., Langlois C. M., Wood E. M., Mim R., Howe S., Ofidis D.. (2025). Evaluation of self-mediated alternatives for risk testing education and return of results (eSMARTER) study: a randomized study of methods for returning APOE and pTau-217 results. Alzheimers Dement 11: e70177. doi:, doi:10.1002/trc2.70177
  25. Fortea J., Pegueroles J., Alcolea D., Belbin O., Dols-Icardo O., Vaqué-Alcázar L.. (2024). APOE4 homozygosity represents a distinct genetic form of Alzheimer’s disease. Nat. Med. 30, 1284 – 1291. doi:, doi:10.1038/s41591-024-02931-w
  26. Genetic Discrimination-National Human Genome Research Institute (2025). National Human Genome Research Institute. Available online at: (accessed December 10, 2025)
  27. Goldman J. S., Hahn S. E., Catania J. W., Larusse-Eckert S., Butson M. B., Rumbaugh M.. (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, 597 – 605. doi:, doi:10.1097/GIM.0b013e31821d69b8
  28. Green R. C., Christensen K. D., Cupples L. A., Relkin N. R., Whitehouse P. J., Royal C. D. M.. (2015). A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer’s disease. Alzheimers Dement. 11, 1222 – 1230. doi:, doi:10.1016/j.jalz.2014.10.014
  29. Green R. C., Roberts J. S., Cupples L. A., Relkin N. R., Whitehouse P. J., Brown T.. (2009). Disclosure of APOE genotype for risk of Alzheimer’s disease. N. Engl. J. Med. 361, 245 – 254. doi:, doi:10.1056/NEJMoa0809578
  30. Grill J. D. (2025). Disclosing Alzheimer biomarkers to motivate brain health Behaviors. JAMA Netw. Open 8: e2545780. doi:, doi:10.1001/jamanetworkopen.2025.45780
  31. Hamilton J. (2025). These scientists found Alzheimer’s in their genes. Here’s what they did next. NPR. Available online at: (accessed December 10, 2025).
  32. Iacono D. (2025). A double-edged sword: ethical and psychological implications of APOE genotype disclosure across the lifespan. Neuroethics 18: 51. doi: doi:10.1007/s12152-025-09624-2
  33. Ison H. E., Mowaswes M., Durst R., Leucker T., Knowles J. W., Brown E. E. (2025). Is it time for a paradigm shift? Inclusion of APOE on genetic dyslipidemia panels. J. Genet. Couns. 34: e1889. doi:, doi:10.1002/jgc4.1889
  34. Joly Y., Dupras C., Pinkesz M., Tovino S. A., Rothstein M. A. (2020). Looking beyond GINA: policy approaches to address genetic discrimination. Annu. Rev. Genomics Hum. Genet. 21, 491 – 507. doi:, doi:10.1146/annurev-genom-111119-011436
  35. Koeller D. R., Uhlmann W. R., Carere D. A., Green R. C., Roberts J. S. Group, for the Pg. S (2017). Utilization of genetic counseling after direct-to-consumer genetic testing: findings from the impact of personal genomics (PGen) study. J. Genet. Couns. 26, 1270 – 1279. doi:, doi:10.1007/s10897-017-0106-7
  36. Langbaum J. B., Bradbury A. R., Egleston B. L., Wood E. M., Langlois C. M., Largent E. A.. (2025). Impact of learning APOE genotype on cognitively unimpaired adults: a pre-screening cohort study of the Alzheimer’s prevention initiative generation study 1. Lancet Healthy Longev. 6: 100778. doi:, doi:10.1016/j.lanhl.2025.100778
  37. Langbaum J. B., Karlawish J., Roberts J. S., Wood E. M., Bradbury A., High N.. (2019). GeneMatch: a novel recruitment registry using at-home APOE genotyping to enhance referrals to Alzheimer’s prevention studies. Alzheimers Dement. 15, 515 – 524. doi:, doi:10.1016/j.jalz.2018.12.007
  38. Largent E. A., Bhardwaj T., Abera M., Stites S. D., Harkins K., Lerner A. J.. (2021). Disclosing genetic risk of Alzheimer’s disease to cognitively unimpaired older adults: findings from the study of knowledge and reactions to APOE testing (SOKRATES II). J. Alzheimer's Dis. 84, 1015 – 1028. doi:, doi:10.3233/JAD-210675
  39. Lineweaver T. T., Bondi M. W., Glasko D., Salmon D. (2014). Effect of knowledge of APOE genotype on subjective and objective memory performance in healthy older adults. Am. J. Psychiatry 171, 201 – 208. doi:, doi:10.1176/appi.ajp.2013.12121590
  40. Marshe V. S., Gorbovskaya I., Kanji S., Kish M., Müller D. J. (2019). Clinical implications of APOE genotyping for late-onset Alzheimer’s disease (LOAD) risk estimation: a review of the literature. J. Neural Transm. 126, 65 – 85. doi:, doi:10.1007/s00702-018-1934-9
  41. Maxmen A. (2017). 23andme given green light to sell DNA tests for 10 diseases. Nature. doi: doi:10.1038/nature.2017.21802
  42. Messner D. A. (2011). Informed choice in direct-to-consumer genetic testing for Alzheimer and other diseases: lessons from two cases. New Genet. Soc. 30, 59 – 72. doi:, doi:10.1080/14636778.2011.552300
  43. Mielke M. M., Fowler N. R. (2024). Alzheimer disease blood biomarkers: considerations for population-level use. Nat. Rev. Neurol. 20, 495 – 504. doi:, doi:10.1038/s41582-024-00989-1
  44. Neergaard L. (2024). New Research Shows People Carrying 2 Copies of a Certain gene are more Likely to have Alzheimer’s. PBS News. Available online at: (accessed January 6, 2026).
  45. Pagano J., Fong J., Wood E., Goldman J., Klee V., Rumbaugh M. (2024). Clinical genetic testing for Alzheimer disease and related dementias. Pract. Neurol. Available online at: (accessed November 18, 2025).
  46. Prince A. E. R. (2019). Political economy, stakeholder voices, and saliency: lessons from international policies regulating insurer use of genetic information. J. Law Biosci. 5, 461 – 494. doi:, doi:10.1093/jlb/lsz001
  47. Qian J., Wolters F. J., Beiser A., Haan M., Ikram M. A., Karlawish J.. (2017). APOE-related risk of mild cognitive impairment and dementia for prevention trials: an analysis of four cohorts. PLoS Med. 14: e1002254. doi:, doi:10.1371/journal.pmed.1002254
  48. Reiman E. M., Ghisays V., Langbaum J. B. (2025). The risk of Alzheimer disease in APOE4 homozygotes. JAMA Neurol. 82, 879 – 880. doi:, doi:10.1001/jamaneurol.2025.0639
  49. Relkin N. R., Kwon Y. J., Tsai J., Gandy S. (1996). The National Institute on Aging/Alzheimer’s association recommendations on the application of apolipoprotein E genotyping to Alzheimer’s disease. Ann. N. Y. Acad. Sci. 802, 149 – 176. doi:, doi:10.1111/j.1749-6632.1996.tb32608.x
  50. Ritchie M., Sajjadi S. A., Grill J. D. (2024). Apolipoprotein E genetic testing in a new age of Alzheimer disease clinical practice. Neurol Clin Pract 14: e200230. doi:, doi:10.1212/CPJ.0000000000200230
  51. Roberts J. S., Chen C. A., Uhlmann W. R., Green R. C. (2012). Effectiveness of a condensed protocol for disclosing APOE genotype and providing risk education for Alzheimer disease. Genet. Med. 14, 742 – 748. doi:, doi:10.1038/gim.2012.37
  52. Rubin R. (2025). What to know about the first FDA-cleared blood test for Alzheimer biomarkers. JAMA 334, 195 – 197. doi:, doi:10.1001/jama.2025.9013
  53. Rumbaugh M., Chan A. K. (2025). “ APOE and genetic Counseling for dementia in clinical practice,” in Apolipoprotein E, (Berlin: Springer), 1 – 26. doi: doi:10.1007/978-3-031-52641-1_71-1
  54. Ryan M. M., Cox C. G., Witbracht M., Hoang D., Gillen D. L., Grill J. D. (2021). Using direct-to-consumer genetic testing results to accelerate Alzheimer disease clinical trial recruitment. Alzheimer Dis. Assoc. Disord. 35, 141 – 147. doi:, doi:10.1097/WAD.0000000000000421
  55. Schonbek A. (2024). The Anxiety Created by 23andMe’s Alzheimer’s Gene Test. Available online at: (accessed November 4, 2025).
  56. Serrano-Pozo A., Das S., Hyman B. T. (2021). APOE and Alzheimer’s disease: advances in genetics, pathophysiology, and therapeutic approaches. Lancet Neurol. 20, 68 – 80. doi:, doi:10.1016/S1474-4422(20)30412-9
  57. Shickh S., Rafferty S. A., Clausen M., Kodida R., Mighton C., Panchal S.. (2021). The role of digital tools in the delivery of genomic medicine: enhancing patient-centered care. Genet. Med. 23, 1086 – 1094. doi:, doi:10.1038/s41436-021-01112-1
  58. Steenhuysen J. (2023). Insight: “It Totally Backfired”: the pitfalls of Alzheimer’s genetic testing. Available online at: (accessed January 6, 2026)
  59. Stites S., Vogt N., Blacker D., Rumbaugh M., Monica P. Advisory Group on Risk Evidence Education for Dementia (AGREED) (2022). Patients asking about APOE gene test results? Here’s what to tell them. J. Fam. Pract. 71, E1 – E7. doi: doi:10.12788/jfp.0397
  60. Sturm A. C., Knowles J. W., Gidding S. S., Ahmad Z. S., Ahmed C. D., Ballantyne C. M.. (2018). Clinical genetic testing for familial hypercholesterolemia. J. Am. Coll. Cardiol. 72, 662 – 680. doi:, doi:10.1016/j.jacc.2018.05.044
  61. Van Cauwenberghe C., Van Broeckhoven C., Sleegers K. (2016). The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genet. Med. 18, 421 – 430. doi:, doi:10.1038/gim.2015.117
  62. van Dyck C. H., Swanson C. J., Aisen P., Bateman R. J., Chen C., Gee M. (2023) Lecanemab in early Alzheimer’s disease N. Engl. J. Med. 388 9 – 21 doi: doi:10.1056/NEJMoa2212948
  63. Waldemar G., Dubois B., Emre M., Georges J., McKeith I. G., Rossor M.. (2007). Recommendations for the diagnosis and management of Alzheimer’s disease and other disorders associated with dementia: EFNS guideline. Eur. J. Neurol. 14, e1 – e26. doi: doi:10.1111/j.1468-1331.2006.01605.x
  64. Wood E., Cacioppo C., Weinberg M., Dratch L., Azage M., Mim R.. (2025). The new landscape of APOE genotyping in the Alzheimer’s clinic: harnessing genetic counseling experience to create digital tools to support patients considering anti-amyloid therapies. Alzheimers Dement. 20: e089364. doi: doi:10.1002/alz.089364
  65. Zallen D. T. (2018). “Well, good luck with that”: reactions to learning of increased genetic risk for Alzheimer disease. Genet. Med. 20, 1462 – 1467. doi:, doi:10.1038/gim.2018.13
  66. Zampatti S., Peconi C., Farro J., Piras F., Pellicano C., Caltagirone C.. (2025). Pharmacogenetics or predictive genetics? APOE testing blurs the lines. Front. Pharmacol. 16: 1627239. doi:, doi:10.3389/fphar.2025.1627239

Citation

Uhlmann, W. R., et al. (2026). Now is the time: the need to update guidance to expand access to APOE genetic testing. Frontiers in Dementia, Volume 5. https://doi.org/
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5 - 2026

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Copyright © 2026 Uhlmann, Chan and Goldman.

License: https://creativecommons.org/licenses/by/4.0/

*Correspondence: Wendy R. Uhlmann

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