23 and me and you Should you test yourself for Alzheimer s and Parkinson s genes? Brain TLC November 2017
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1 23 and me and you Should you test yourself for Alzheimer s and Parkinson s genes? Brain TLC November 2017
2 disclosures Dr. Quinn has no financial conflict of interest related to this topic. (eg, no financial relationship with 23 and me ) Dr. Quinn does research on gene carriers with and without Parkinson s disease. That research would be facilitated by patients learning their genotypes.
3 Issues to review around genetic testing: What do we know about genes for Alzheimer s and Parkinson s? Can doctors order genetic tests? Should they? Can you really order the tests yourself? What kind of research is taking place in this area?
4 Issues to review around genetic testing: What do we know about genes for Alzheimer s and Parkinson s? Can doctors order genetic tests? Should they? Can you really order the tests yourself? What kind of research is taking place in this area?
5 Alzheimer s: a disease characterized by dementia, plaques, and tangles
6 Two types of genes in Alzheimer s disease Genes that cause Alzheimer s: Genes that modify the risk of Alzheimer s:
7 Genes in Alzheimer s disease Genes that cause Alzheimer s: Half of every generation affected Early onset: 40s or even younger Very rare
8 Genes in Alzheimer s disease Genes that cause Alzheimer s:
9 Genes in Alzheimer s disease Genes that cause Alzheimer s: APP Presenilin-1 Presenilin-2 Other unknown genes
10 Genes in Alzheimer s disease Genes that modify the risk of Alzheimer s: Apolipoprotein E ApoE Discovered as a risk factor for Alzheimer s in 1993 Comes in 3 versions: E2, E3, E4 3/3 is most common. E4 increases risk of Alzheimer s E2 reduces risk of Alzheimer s Each person has two copies of the gene Can be 2/2, 2/3, 2/4, 3/3, 3/4, 4/4
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12 Genes in Alzheimer s disease Genes that modify the risk of Alzheimer s: Apolipoprotein E ApoE 15-20% of the healthy control population has at least one copy of E4 50% of Alzheimer s patients have at least one copy of E4 So: You can have Alzheimer s without having the gene You can also have the gene and never get Alzheimer s
13 Other genes that modify the risk of Alzheimer s Nature Genetics 41, (2009) doi: /ng.440
14 Genes that modify the risk of Alzheimer s Table 1: Late-onset Alzheimer s disease associated genes/variants. Variant Gene Abbreviation Risk/protective rs7412 Apolipoprotein E APOE Risk rs Apolipoprotein E APOE Protective rs Bridging integrator 1 BIN1 Risk rs Clusterin CLU Protective rs ATP-binding cassette, subfamily A (ABC1), member 7 ABCA7 Risk rs Complement component (3b/4b) receptor 1 (Knops blood group) CR1 Risk rs Phosphatidylinositol binding clathrin assembly protein PICALM Protective rs Membrane-spanning 4 domains, subfamily A, member 6A MS4A6A Protective rs CD33 molecule CD33 Protective rs Membrane-spanning 4 domains, subfamily A, member 4E MS4A4E Risk rs CD2-associated protein CD2AP Risk Each of the top variants associated with late-onset Alzheimer s disease from metaanalysis done by the Alzheimer Research Forum is listed here, together with the specific associated variant, and whether the variant increases risk or provides protection.
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18 But The ApoE gene has the strongest effect on Alzheimer s risk Alzheimer gene panels are not offered at present
19 Issues to review around genetic testing: What do we know about genes for Alzheimer s and Parkinson s? Can doctors order genetic tests? Should they? Can you really order the tests yourself? What kind of research is taking place in this area?
20 Can you get tested? Doctors can order the ApoE test on people who have a diagnosis. Doctors can order the ApoE test on people at risk but this should always be done with genetic counseling before and after testing. Cost = about $400 Insurance coverage varies
21 Should you get tested?
22 Should you get tested?
23 Should you get tested for Alzheimer s genes? No: The predictive value is not good No: Knowing the genotype does not lead to a particular treatment. No: learning of a positive test result without genetic counseling may cause significant anxiety No: if the results leak out it could result in job discrimination or other adverse events
24 Issues to review around genetic testing: What do we know about genes for Alzheimer s and Parkinson s? Can doctors order genetic tests? Should they? Can you really order the tests yourself? What kind of research is taking place in this area?
25 Can you get tested anyway? You can also do-it-yourself with 23 and me.
26 Can you get tested anyway? You can also do-it-yourself with 23 and me. order a kit on line Pay $199 They send a tube to spit into and a mailing package You send it back and then they you some health questions. They send you a report with information on your genetic ancestry, ApoE4 results, and several pieces of obscure genetic information. They do not test for non ApoE4 genes for Alzheimer s. They also test for two genes related to Parkinson s disease.
27 Parkinson s disease
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30 Genes associated with Parkinson s:
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32 Most common genes for Parkinson s: LRRK2: about 1% of patients with Parkinson s disease GBA: about 4% of patients with Parkinson s disease
33 Can you get tested? Doctors can order the LRRK2 and GBA tests on people who have a diagnosis. Doctors can order the tests on people at risk but this should always be done with genetic counseling before and after testing. Cost= about $400 per test Insurance coverage varies
34 Should you get tested for Parkinson s genes? No: The predictive value is not good No: Knowing the genotype does not lead to a particular treatment**. No: learning of a positive test result without genetic counseling may cause significant anxiety No: if the results leak out it could result in job discrimination or other adverse events
35 Can you get tested anyway? You can also do-it-yourself with 23 and me. order a kit on line Pay $200 They send a tube to spit into and a mailing package You send it back and then they you some health questions. A few weeks later, they send you a report with information on your genetic ancestry, ApoE4, LRRK2 and GBA results, and several pieces of obscure genetic information.
36 23 and me the doctor s perspective : People got tested by 23 and me and received results sent directly to them They would bring reports in to me and I struggled to interpret them. 2013: The FDA ordered them to stop testing. April 2017: The FDA permitted 23 and me to resume offering directto-consumer genetic testing for Alzheimer s and Parkinson s. I was asked to comment by a couple of media outlets and I expressed my concern that people were going to get genetic information that they would be hard-pressed to interpret.
37 23 and me the patient s perspective Sept-October 2017: I tested myself at 23 and me so I could understand the patient experience. 9/20/17-registered on the internet-paid $199 9/27/17 put my spit in the mail 10/4/17 questions regarding Alzheimer s and Parkinson s 10/5/17 your sample has reached the lab 10/22/17 your reports are ready
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60 Consider: What if I tested positive? Would probably not have shared that publicly. May have caused significant anxiety
61 Issues to review around genetic testing: What do we know about genes for Alzheimer s and Parkinson s? Can doctors order genetic tests? Should they? Can you really order the tests yourself? What kind of research is taking place in this area?
62 Two studies at OHSU: 1) Pacific Udall Study: NIH-funded study of cognitive decline and dementia in Parkinson s disease. Compares ApoE4 carriers, GBA carriers, and non-carriers with and without Parkinson s. 2) Moves-PD: study of a drug targeting the GBA pathway, confined to patients with Parkinson s disease who are GBA carriers.
63 Two studies at OHSU: 1) Pacific Udall Study: NIH-funded study of cognitive decline and dementia in Parkinson s disease. Compares ApoE4 carriers, GBA carriers, and non-carriers with and without Parkinson s. Participants have neuropsychological testing every two years. If interested and eligible, participants may also participate in a study involving transcranial magnetic stimulation as a way to probe neurotransmitters in the brain. Highly motivated participants can also travel to UW in Seattle to participate in a functional MRI study.
64 Two studies at OHSU: 2) Moves-PD: study of a drug targeting the GBA pathway, confined to patients with Parkinson s disease who are GBA carriers.
65 Two studies at OHSU: 2) Moves-PD: study of a drug targeting the GBA pathway, confined to patients with Parkinson s disease who are GBA carriers. GBA pathway: GBA enzyme A B C D
66 Two studies at OHSU: 2) Moves-PD: study of a drug targeting the GBA pathway, confined to patients with Parkinson s disease who are GBA carriers. GBA pathway: GBA mutation A B C D
67 Two studies at OHSU: 2) Moves-PD: study of a drug targeting the GBA pathway, confined to patients with Parkinson s disease who are GBA carriers. GBA pathway: GBA mutation A B C D toxicity
68 Two studies at OHSU: 2) Moves-PD: study of a drug targeting the GBA pathway, confined to patients with Parkinson s disease who are GBA carriers. GBA pathway: drug GBA mutation A B C D No toxicity
69 GBA study for Parkinson s: Genotype patients with Parkinson s disease Enroll only those Parkinson s patients who are GBA carriers Randomize to GBA pathway drug vs placebo See if the rate of disease progression is slower in patients on active drug
70 Two studies at OHSU: 1) Pacific Udall Study: NIH-funded study of cognitive decline and dementia in Parkinson s disease. Compares ApoE4 carriers, GBA carriers, and non-carriers with and without Parkinson s. 2) Moves-PD: study of a drug targeting the GBA pathway, confined to patients with Parkinson s disease who are GBA carriers. Interested parties should contact Dr Quinn at quinnj@ohsu.edu
71 Montine et al, Am J Pathology 2016
72 Montine et al, Am J Pathology 2016
73 Thank you for your attention Questions?
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