Presence of an APOE4 allele results in significantly earlier onset of Parkinson's disease and a higher risk with dementia

Nathan Pankratz; Lisa Byder; Cheryl Halter; Alice Rudolph; Clifford W. Shults; P. Michael Conneally; Tatiana Foroud; William C. Nichols; Kelly Lyons; Karen Marder; Frederick Marshall; David Oakes; Alice Rudolph; Aileen Shinaman; Eric Siemers; Joanne Wojcieszek; Jo Belden; Julie Carter; Richard Camicioli; Pam Andrews; Michel Panisset; Jean Hall; Jean Hubble; Magali Fernandez; Carson Reider; Ali Rajput; Alex Rajput; Theresa Shirley; Tilak Mendis; David A. Grimes; Peggy Gray; Carmen Serrano Ramos; Sandra Roque; Ronald Pfeiffer; Brenda Pfeiffer; Lawrence Elmer; Kathy Davis; Joseph Friedman; Hubert Fernandez; Margaret Lannon; Stephen Reich; Becky Dunlop; Lauren Seeberger; Christopher O'Brien; Deborah Judd; Robert Hauser; Theresa Zesiewicz; Holly Delgado; Deborah Fontaine; Danna Jennings; Kenneth Marek; Susan Mendick; Michael Aminoff; Mariann DiMinno; Peter Lewitt; Maryan De Angelis; Rajesh Pahwa; Stephanie Thomas; Daniel Truong; Mayank Pathak; An Tran; Robert Rodnitzky; Judith Dobson; William Koller; William Weiner; Kelly Lyons; Roger Kurlan; Debra Berry; John Bertoni; Carolyn Peterson; Wayne Martin; Marguerite Wieler; Paul Tuite; Robyn Schacherer; Juliette Harris; Joseph Jankovic; Christine Hunter; Anthony Lang; Galit Kleimer-Fisman; Anette Nieves; Julie So; Stewart Factor; Sharon Evans; Bala Manyam; Brian Wulbrecht; Francis Walker; Victoria Hunt; Mark F. Gordon; Joanna Hamman; Un Jung Kang; Joan Young; Karen Blindauer; Jeannine Petit; Jayaraman Rao; Maureen Cook; Mark Stacy; Kelli Williamson; Rachel Saunders Pullman; Karyn Boyar

doi:10.1002/mds.20663

Presence of an APOE4 allele results in significantly earlier onset of Parkinson's disease and a higher risk with dementia

Nathan Pankratz, Lisa Byder, Cheryl Halter, Alice Rudolph, Clifford W. Shults, P. Michael Conneally, Tatiana Foroud, William C. Nichols, Kelly Lyons, Karen Marder, Frederick Marshall, David Oakes, Alice Rudolph, Aileen Shinaman, Eric Siemers, Joanne Wojcieszek, Jo Belden, Julie Carter, Richard Camicioli, Pam AndrewsMichel Panisset, Jean Hall, Jean Hubble, Magali Fernandez, Carson Reider, Ali Rajput, Alex Rajput, Theresa Shirley, Tilak Mendis, David A. Grimes, Peggy Gray, Carmen Serrano Ramos, Sandra Roque, Ronald Pfeiffer, Brenda Pfeiffer, Lawrence Elmer, Kathy Davis, Joseph Friedman, Hubert Fernandez, Margaret Lannon, Stephen Reich, Becky Dunlop, Lauren Seeberger, Christopher O'Brien, Deborah Judd, Robert Hauser, Theresa Zesiewicz, Holly Delgado, Deborah Fontaine, Danna Jennings, Kenneth Marek, Susan Mendick, Michael Aminoff, Mariann DiMinno, Peter Lewitt, Maryan De Angelis, Rajesh Pahwa, Stephanie Thomas, Daniel Truong, Mayank Pathak, An Tran, Robert Rodnitzky, Judith Dobson, William Koller, William Weiner, Kelly Lyons, Roger Kurlan, Debra Berry, John Bertoni, Carolyn Peterson, Wayne Martin, Marguerite Wieler, Paul Tuite, Robyn Schacherer, Juliette Harris, Joseph Jankovic, Christine Hunter, Anthony Lang, Galit Kleimer-Fisman, Anette Nieves, Julie So, Stewart Factor, Sharon Evans, Bala Manyam, Brian Wulbrecht, Francis Walker, Victoria Hunt, Mark F. Gordon, Joanna Hamman, Un Jung Kang, Joan Young, Karen Blindauer, Jeannine Petit, Jayaraman Rao, Maureen Cook, Mark Stacy, Kelli Williamson, Rachel Saunders Pullman, Karyn Boyar

Neurology

Research output: Contribution to journal › Article › peer-review

88 Scopus citations

Abstract

The ε4 allele of the apolipoprotein E gene (APOE4) has been consistently associated with a greater risk of Alzheimer's disease (AD) as well as an earlier onset of AD. It is possible that APOE4 may also play a role in the etiology of other neurodegenerative disorders, such as Parkinson's disease (PD). APOE genotype, age of onset, disease duration, smoking history, and dementia status were collected for families with PD, yielding 324 Caucasian families with complete information. Logistic regression employing one individual per family and including age of onset and disease duration as covariates demonstrated a significantly increased risk of dementia for those individuals having inherited at least one ε4 allele (OR = 3.37; P = 0.002). Survival analyses also demonstrated a significantly earlier age of onset for those subjects with at least one ε4 allele (59.7 years) as compared with those homozygous for the more common ε3 allele (62.4 years; P = 0.009). Thus, consistent with previous studies, we find evidence that the presence of an ε4 allele results in significantly earlier onset of PD and a greater likelihood of dementia. It appears the similarities between PD and AD may be due to an overlap in the diseases' genetic etiology.

Original language	English (US)
Pages (from-to)	45-49
Number of pages	5
Journal	Movement Disorders
Volume	21
Issue number	1
DOIs	https://doi.org/10.1002/mds.20663
State	Published - Jan 2006

Keywords

Age of onset
Apolipoprotein E
Dementia
Parkinson's disease

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1002/mds.20663

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Pankratz, N., Byder, L., Halter, C., Rudolph, A., Shults, C. W., Conneally, P. M., Foroud, T., Nichols, W. C., Lyons, K., Marder, K., Marshall, F., Oakes, D., Rudolph, A., Shinaman, A., Siemers, E., Wojcieszek, J., Belden, J., Carter, J., Camicioli, R., ... Boyar, K. (2006). Presence of an APOE4 allele results in significantly earlier onset of Parkinson's disease and a higher risk with dementia. Movement Disorders, 21(1), 45-49. https://doi.org/10.1002/mds.20663

Pankratz, N, Byder, L, Halter, C, Rudolph, A, Shults, CW, Conneally, PM, Foroud, T, Nichols, WC, Lyons, K, Marder, K, Marshall, F, Oakes, D, Rudolph, A, Shinaman, A, Siemers, E, Wojcieszek, J, Belden, J, Carter, J, Camicioli, R, Andrews, P, Panisset, M, Hall, J, Hubble, J, Fernandez, M, Reider, C, Rajput, A, Rajput, A, Shirley, T, Mendis, T, Grimes, DA, Gray, P, Ramos, CS, Roque, S, Pfeiffer, R, Pfeiffer, B, Elmer, L, Davis, K, Friedman, J, Fernandez, H, Lannon, M, Reich, S, Dunlop, B, Seeberger, L, O'Brien, C, Judd, D, Hauser, R, Zesiewicz, T, Delgado, H, Fontaine, D, Jennings, D, Marek, K, Mendick, S, Aminoff, M, DiMinno, M, Lewitt, P, De Angelis, M, Pahwa, R, Thomas, S, Truong, D, Pathak, M, Tran, A, Rodnitzky, R, Dobson, J, Koller, W, Weiner, W, Lyons, K, Kurlan, R, Berry, D, Bertoni, J, Peterson, C, Martin, W, Wieler, M, Tuite, P, Schacherer, R, Harris, J, Jankovic, J, Hunter, C, Lang, A, Kleimer-Fisman, G, Nieves, A, So, J, Factor, S, Evans, S, Manyam, B, Wulbrecht, B, Walker, F, Hunt, V, Gordon, MF, Hamman, J, Kang, UJ, Young, J, Blindauer, K, Petit, J, Rao, J, Cook, M, Stacy, M, Williamson, K, Pullman, RS & Boyar, K 2006, 'Presence of an APOE4 allele results in significantly earlier onset of Parkinson's disease and a higher risk with dementia', Movement Disorders, vol. 21, no. 1, pp. 45-49. https://doi.org/10.1002/mds.20663

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title = "Presence of an APOE4 allele results in significantly earlier onset of Parkinson's disease and a higher risk with dementia",

abstract = "The ε4 allele of the apolipoprotein E gene (APOE4) has been consistently associated with a greater risk of Alzheimer's disease (AD) as well as an earlier onset of AD. It is possible that APOE4 may also play a role in the etiology of other neurodegenerative disorders, such as Parkinson's disease (PD). APOE genotype, age of onset, disease duration, smoking history, and dementia status were collected for families with PD, yielding 324 Caucasian families with complete information. Logistic regression employing one individual per family and including age of onset and disease duration as covariates demonstrated a significantly increased risk of dementia for those individuals having inherited at least one ε4 allele (OR = 3.37; P = 0.002). Survival analyses also demonstrated a significantly earlier age of onset for those subjects with at least one ε4 allele (59.7 years) as compared with those homozygous for the more common ε3 allele (62.4 years; P = 0.009). Thus, consistent with previous studies, we find evidence that the presence of an ε4 allele results in significantly earlier onset of PD and a greater likelihood of dementia. It appears the similarities between PD and AD may be due to an overlap in the diseases' genetic etiology.",

keywords = "Age of onset, Apolipoprotein E, Dementia, Parkinson's disease",

author = "Nathan Pankratz and Lisa Byder and Cheryl Halter and Alice Rudolph and Shults, {Clifford W.} and Conneally, {P. Michael} and Tatiana Foroud and Nichols, {William C.} and Kelly Lyons and Karen Marder and Frederick Marshall and David Oakes and Alice Rudolph and Aileen Shinaman and Eric Siemers and Joanne Wojcieszek and Jo Belden and Julie Carter and Richard Camicioli and Pam Andrews and Michel Panisset and Jean Hall and Jean Hubble and Magali Fernandez and Carson Reider and Ali Rajput and Alex Rajput and Theresa Shirley and Tilak Mendis and Grimes, {David A.} and Peggy Gray and Ramos, {Carmen Serrano} and Sandra Roque and Ronald Pfeiffer and Brenda Pfeiffer and Lawrence Elmer and Kathy Davis and Joseph Friedman and Hubert Fernandez and Margaret Lannon and Stephen Reich and Becky Dunlop and Lauren Seeberger and Christopher O'Brien and Deborah Judd and Robert Hauser and Theresa Zesiewicz and Holly Delgado and Deborah Fontaine and Danna Jennings and Kenneth Marek and Susan Mendick and Michael Aminoff and Mariann DiMinno and Peter Lewitt and {De Angelis}, Maryan and Rajesh Pahwa and Stephanie Thomas and Daniel Truong and Mayank Pathak and An Tran and Robert Rodnitzky and Judith Dobson and William Koller and William Weiner and Kelly Lyons and Roger Kurlan and Debra Berry and John Bertoni and Carolyn Peterson and Wayne Martin and Marguerite Wieler and Paul Tuite and Robyn Schacherer and Juliette Harris and Joseph Jankovic and Christine Hunter and Anthony Lang and Galit Kleimer-Fisman and Anette Nieves and Julie So and Stewart Factor and Sharon Evans and Bala Manyam and Brian Wulbrecht and Francis Walker and Victoria Hunt and Gordon, {Mark F.} and Joanna Hamman and Kang, {Un Jung} and Joan Young and Karen Blindauer and Jeannine Petit and Jayaraman Rao and Maureen Cook and Mark Stacy and Kelli Williamson and Pullman, {Rachel Saunders} and Karyn Boyar",

year = "2006",

month = jan,

doi = "10.1002/mds.20663",

language = "English (US)",

volume = "21",

pages = "45--49",

journal = "Movement Disorders",

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AU - Pankratz, Nathan

AU - Byder, Lisa

AU - Halter, Cheryl

AU - Rudolph, Alice

AU - Shults, Clifford W.

AU - Conneally, P. Michael

AU - Foroud, Tatiana

AU - Nichols, William C.

AU - Lyons, Kelly

AU - Marder, Karen

AU - Marshall, Frederick

AU - Oakes, David

AU - Rudolph, Alice

AU - Shinaman, Aileen

AU - Siemers, Eric

AU - Wojcieszek, Joanne

AU - Belden, Jo

AU - Carter, Julie

AU - Camicioli, Richard

AU - Andrews, Pam

AU - Panisset, Michel

AU - Hall, Jean

AU - Hubble, Jean

AU - Fernandez, Magali

AU - Reider, Carson

AU - Rajput, Ali

AU - Rajput, Alex

AU - Shirley, Theresa

AU - Mendis, Tilak

AU - Grimes, David A.

AU - Gray, Peggy

AU - Ramos, Carmen Serrano

AU - Roque, Sandra

AU - Pfeiffer, Ronald

AU - Pfeiffer, Brenda

AU - Elmer, Lawrence

AU - Davis, Kathy

AU - Friedman, Joseph

AU - Fernandez, Hubert

AU - Lannon, Margaret

AU - Reich, Stephen

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AU - Seeberger, Lauren

AU - O'Brien, Christopher

AU - Judd, Deborah

AU - Hauser, Robert

AU - Zesiewicz, Theresa

AU - Delgado, Holly

AU - Fontaine, Deborah

AU - Jennings, Danna

AU - Marek, Kenneth

AU - Mendick, Susan

AU - Aminoff, Michael

AU - DiMinno, Mariann

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AU - Truong, Daniel

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AU - Tran, An

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AU - Koller, William

AU - Weiner, William

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AU - Berry, Debra

AU - Bertoni, John

AU - Peterson, Carolyn

AU - Martin, Wayne

AU - Wieler, Marguerite

AU - Tuite, Paul

AU - Schacherer, Robyn

AU - Harris, Juliette

AU - Jankovic, Joseph

AU - Hunter, Christine

AU - Lang, Anthony

AU - Kleimer-Fisman, Galit

AU - Nieves, Anette

AU - So, Julie

AU - Factor, Stewart

AU - Evans, Sharon

AU - Manyam, Bala

AU - Wulbrecht, Brian

AU - Walker, Francis

AU - Hunt, Victoria

AU - Gordon, Mark F.

AU - Hamman, Joanna

AU - Kang, Un Jung

AU - Young, Joan

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AU - Rao, Jayaraman

AU - Cook, Maureen

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AU - Williamson, Kelli

AU - Pullman, Rachel Saunders

AU - Boyar, Karyn

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N2 - The ε4 allele of the apolipoprotein E gene (APOE4) has been consistently associated with a greater risk of Alzheimer's disease (AD) as well as an earlier onset of AD. It is possible that APOE4 may also play a role in the etiology of other neurodegenerative disorders, such as Parkinson's disease (PD). APOE genotype, age of onset, disease duration, smoking history, and dementia status were collected for families with PD, yielding 324 Caucasian families with complete information. Logistic regression employing one individual per family and including age of onset and disease duration as covariates demonstrated a significantly increased risk of dementia for those individuals having inherited at least one ε4 allele (OR = 3.37; P = 0.002). Survival analyses also demonstrated a significantly earlier age of onset for those subjects with at least one ε4 allele (59.7 years) as compared with those homozygous for the more common ε3 allele (62.4 years; P = 0.009). Thus, consistent with previous studies, we find evidence that the presence of an ε4 allele results in significantly earlier onset of PD and a greater likelihood of dementia. It appears the similarities between PD and AD may be due to an overlap in the diseases' genetic etiology.

AB - The ε4 allele of the apolipoprotein E gene (APOE4) has been consistently associated with a greater risk of Alzheimer's disease (AD) as well as an earlier onset of AD. It is possible that APOE4 may also play a role in the etiology of other neurodegenerative disorders, such as Parkinson's disease (PD). APOE genotype, age of onset, disease duration, smoking history, and dementia status were collected for families with PD, yielding 324 Caucasian families with complete information. Logistic regression employing one individual per family and including age of onset and disease duration as covariates demonstrated a significantly increased risk of dementia for those individuals having inherited at least one ε4 allele (OR = 3.37; P = 0.002). Survival analyses also demonstrated a significantly earlier age of onset for those subjects with at least one ε4 allele (59.7 years) as compared with those homozygous for the more common ε3 allele (62.4 years; P = 0.009). Thus, consistent with previous studies, we find evidence that the presence of an ε4 allele results in significantly earlier onset of PD and a greater likelihood of dementia. It appears the similarities between PD and AD may be due to an overlap in the diseases' genetic etiology.

KW - Age of onset

KW - Apolipoprotein E

KW - Dementia

KW - Parkinson's disease

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JO - Movement Disorders

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Presence of an APOE4 allele results in significantly earlier onset of Parkinson's disease and a higher risk with dementia

Abstract

Keywords

ASJC Scopus subject areas

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