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

Research output: Contribution to journalArticle

64 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)45-49
Number of pages5
JournalMovement Disorders
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2006

Fingerprint

Parkinson Disease
Dementia
Alleles
Age of Onset
Alzheimer Disease
Apolipoprotein E4
Inborn Genetic Diseases
Survival Analysis
Neurodegenerative Diseases
Logistic Models
Smoking
History
Genotype
Genes

Keywords

  • Age of onset
  • Apolipoprotein E
  • Dementia
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Pankratz, N., Byder, L., Halter, C., Rudolph, A., Shults, C. W., Conneally, P. M., ... 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

Presence of an APOE4 allele results in significantly earlier onset of Parkinson's disease and a higher risk with dementia. / Pankratz, Nathan; Byder, Lisa; Halter, Cheryl; Rudolph, Alice; Shults, Clifford W.; Conneally, P. Michael; Foroud, Tatiana; Nichols, William C.; Lyons, Kelly; Marder, Karen; Marshall, Frederick; Oakes, David; Rudolph, Alice; Shinaman, Aileen; Siemers, Eric; Wojcieszek, Joanne; Belden, Jo; Carter, Julie; Camicioli, Richard; Andrews, Pam; Panisset, Michel; Hall, Jean; Hubble, Jean; Fernandez, Magali; Reider, Carson; Rajput, Ali; Rajput, Alex; Shirley, Theresa; Mendis, Tilak; Grimes, David A.; Gray, Peggy; Ramos, Carmen Serrano; Roque, Sandra; Pfeiffer, Ronald; Pfeiffer, Brenda; Elmer, Lawrence; Davis, Kathy; Friedman, Joseph; Fernandez, Hubert; Lannon, Margaret; Reich, Stephen; Dunlop, Becky; Seeberger, Lauren; O'Brien, Christopher; Judd, Deborah; Hauser, Robert; Zesiewicz, Theresa; Delgado, Holly; Fontaine, Deborah; Jennings, Danna; Marek, Kenneth; Mendick, Susan; Aminoff, Michael; DiMinno, Mariann; Lewitt, Peter; De Angelis, Maryan; Pahwa, Rajesh; Thomas, Stephanie; Truong, Daniel; Pathak, Mayank; Tran, An; Rodnitzky, Robert; Dobson, Judith; Koller, William; Weiner, William; Lyons, Kelly; Kurlan, Roger; Berry, Debra; Bertoni, John; Peterson, Carolyn; Martin, Wayne; Wieler, Marguerite; Tuite, Paul; Schacherer, Robyn; Harris, Juliette; Jankovic, Joseph; Hunter, Christine; Lang, Anthony; Kleimer-Fisman, Galit; Nieves, Anette; So, Julie; Factor, Stewart; Evans, Sharon; Manyam, Bala; Wulbrecht, Brian; Walker, Francis; Hunt, Victoria; Gordon, Mark F.; Hamman, Joanna; Kang, Un Jung; Young, Joan; Blindauer, Karen; Petit, Jeannine; Rao, Jayaraman; Cook, Maureen; Stacy, Mark; Williamson, Kelli; Pullman, Rachel Saunders; Boyar, Karyn.

In: Movement Disorders, Vol. 21, No. 1, 01.01.2006, p. 45-49.

Research output: Contribution to journalArticle

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
Pankratz, Nathan ; Byder, Lisa ; Halter, Cheryl ; Rudolph, Alice ; Shults, Clifford W. ; Conneally, P. Michael ; Foroud, Tatiana ; Nichols, William C. ; Lyons, Kelly ; Marder, Karen ; Marshall, Frederick ; Oakes, David ; Rudolph, Alice ; Shinaman, Aileen ; Siemers, Eric ; Wojcieszek, Joanne ; Belden, Jo ; Carter, Julie ; Camicioli, Richard ; Andrews, Pam ; Panisset, Michel ; Hall, Jean ; Hubble, Jean ; Fernandez, Magali ; Reider, Carson ; Rajput, Ali ; Rajput, Alex ; Shirley, Theresa ; Mendis, Tilak ; Grimes, David A. ; Gray, Peggy ; Ramos, Carmen Serrano ; Roque, Sandra ; Pfeiffer, Ronald ; Pfeiffer, Brenda ; Elmer, Lawrence ; Davis, Kathy ; Friedman, Joseph ; Fernandez, Hubert ; Lannon, Margaret ; Reich, Stephen ; Dunlop, Becky ; Seeberger, Lauren ; O'Brien, Christopher ; Judd, Deborah ; Hauser, Robert ; Zesiewicz, Theresa ; Delgado, Holly ; Fontaine, Deborah ; Jennings, Danna ; Marek, Kenneth ; Mendick, Susan ; Aminoff, Michael ; DiMinno, Mariann ; Lewitt, Peter ; De Angelis, Maryan ; Pahwa, Rajesh ; Thomas, Stephanie ; Truong, Daniel ; Pathak, Mayank ; Tran, An ; Rodnitzky, Robert ; Dobson, Judith ; Koller, William ; Weiner, William ; Lyons, Kelly ; Kurlan, Roger ; Berry, Debra ; Bertoni, John ; Peterson, Carolyn ; Martin, Wayne ; Wieler, Marguerite ; Tuite, Paul ; Schacherer, Robyn ; Harris, Juliette ; Jankovic, Joseph ; Hunter, Christine ; Lang, Anthony ; Kleimer-Fisman, Galit ; Nieves, Anette ; So, Julie ; Factor, Stewart ; Evans, Sharon ; Manyam, Bala ; Wulbrecht, Brian ; Walker, Francis ; Hunt, Victoria ; Gordon, Mark F. ; Hamman, Joanna ; Kang, Un Jung ; Young, Joan ; Blindauer, Karen ; Petit, Jeannine ; Rao, Jayaraman ; Cook, Maureen ; Stacy, Mark ; Williamson, Kelli ; Pullman, Rachel Saunders ; Boyar, Karyn. / Presence of an APOE4 allele results in significantly earlier onset of Parkinson's disease and a higher risk with dementia. In: Movement Disorders. 2006 ; Vol. 21, No. 1. pp. 45-49.
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AU - Byder, Lisa

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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

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AU - Pfeiffer, Ronald

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AU - Elmer, Lawrence

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AU - Lannon, Margaret

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AU - Jennings, Danna

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AU - Tuite, Paul

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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

AU - Blindauer, Karen

AU - Petit, Jeannine

AU - Rao, Jayaraman

AU - Cook, Maureen

AU - Stacy, Mark

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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