Effect of GBA1 Mutations and APOE Polymorphisms on Survival and Progression Among Ashkenazi Jews with Dementia with Lewy Bodies

Tamara Shiner; Gitit Kavé; Anat Mirelman; Keren Regev; Yoav Piura; Orly Goldstein; Mali Gana Weisz; Anat Bar-Shira; Tanya Gurevich; Avi Orr-Urtreger; Roy N Alcalay; Nir Giladi; Noa Bregman

doi:10.1002/mds.30003

Effect of GBA1 Mutations and APOE Polymorphisms on Survival and Progression Among Ashkenazi Jews with Dementia with Lewy Bodies

Tamara Shiner, Gitit Kavé, Anat Mirelman, Keren Regev, Yoav Piura, Orly Goldstein, Mali Gana Weisz, Anat Bar-Shira, Tanya Gurevich, Avi Orr-Urtreger, Roy N Alcalay, Nir Giladi, Noa Bregman

Department of Education and Psychology

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

Abstract

BACKGROUND: Glucocerebrosidase 1 (GBA1) mutations are associated with reduced survival in Parkinson's disease but their effect on survival in dementia with Lewy bodies (DLB) is unclear.

OBJECTIVE: To assess the impact of GBA1 mutations on survival among Ashkenazi Jews with DLB, while controlling for APOE status.

METHODS: One hundred and forty participants from Tel Aviv Medical Center, Israel were genotyped for GBA1 mutations and APOE polymorphisms. Survival rates and follow-up cognitive screening scores were analyzed.

RESULTS: GBA1 mutation carriers had a two-fold increased risk of death (HR = 1.999), while APOE status did not independently affect survival. In a subset of patients with available clinical data (N = 63), carriers of the APOE ε4 allele showed faster cognitive deterioration, while GBA1 mutation carriers also declined more rapidly albeit not significantly.

CONCLUSION: Understanding the genetic effects on survival and progression is crucial for patient counseling and inclusion in clinical trials.

Original language	English
Pages (from-to)	2280-2285
Number of pages	6
Journal	Movement Disorders
Volume	39
Issue number	12
Early online date	30 Aug 2024
DOIs	https://doi.org/10.1002/mds.30003
State	Published - Dec 2024

Bibliographical note

Keywords

Aged
Aged, 80 and over
Apolipoproteins E/genetics
Disease Progression
Female
Genotype
Glucosylceramidase/genetics
Humans
Israel
Jews/genetics
Lewy Body Disease/genetics
Male
Middle Aged
Mutation/genetics
Polymorphism, Genetic/genetics

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Shiner, T., Kavé, G., Mirelman, A., Regev, K., Piura, Y., Goldstein, O., Gana Weisz, M., Bar-Shira, A., Gurevich, T., Orr-Urtreger, A., Alcalay, R. N., Giladi, N., & Bregman, N. (2024). Effect of GBA1 Mutations and APOE Polymorphisms on Survival and Progression Among Ashkenazi Jews with Dementia with Lewy Bodies. Movement Disorders, 39(12), 2280-2285. https://doi.org/10.1002/mds.30003

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title = "Effect of GBA1 Mutations and APOE Polymorphisms on Survival and Progression Among Ashkenazi Jews with Dementia with Lewy Bodies",

abstract = "BACKGROUND: Glucocerebrosidase 1 (GBA1) mutations are associated with reduced survival in Parkinson's disease but their effect on survival in dementia with Lewy bodies (DLB) is unclear.OBJECTIVE: To assess the impact of GBA1 mutations on survival among Ashkenazi Jews with DLB, while controlling for APOE status.METHODS: One hundred and forty participants from Tel Aviv Medical Center, Israel were genotyped for GBA1 mutations and APOE polymorphisms. Survival rates and follow-up cognitive screening scores were analyzed.RESULTS: GBA1 mutation carriers had a two-fold increased risk of death (HR = 1.999), while APOE status did not independently affect survival. In a subset of patients with available clinical data (N = 63), carriers of the APOE ε4 allele showed faster cognitive deterioration, while GBA1 mutation carriers also declined more rapidly albeit not significantly.CONCLUSION: Understanding the genetic effects on survival and progression is crucial for patient counseling and inclusion in clinical trials.",

keywords = "Aged, Aged, 80 and over, Apolipoproteins E/genetics, Disease Progression, Female, Genotype, Glucosylceramidase/genetics, Humans, Israel, Jews/genetics, Lewy Body Disease/genetics, Male, Middle Aged, Mutation/genetics, Polymorphism, Genetic/genetics",

author = "Tamara Shiner and Gitit Kav{\'e} and Anat Mirelman and Keren Regev and Yoav Piura and Orly Goldstein and {Gana Weisz}, Mali and Anat Bar-Shira and Tanya Gurevich and Avi Orr-Urtreger and Alcalay, {Roy N} and Nir Giladi and Noa Bregman",

note = "{\textcopyright} 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.",

year = "2024",

month = dec,

doi = "10.1002/mds.30003",

language = "אנגלית",

volume = "39",

pages = "2280--2285",

journal = "Movement Disorders",

issn = "0885-3185",

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Shiner, T, Kavé, G, Mirelman, A, Regev, K, Piura, Y, Goldstein, O, Gana Weisz, M, Bar-Shira, A, Gurevich, T, Orr-Urtreger, A, Alcalay, RN, Giladi, N & Bregman, N 2024, 'Effect of GBA1 Mutations and APOE Polymorphisms on Survival and Progression Among Ashkenazi Jews with Dementia with Lewy Bodies', Movement Disorders, vol. 39, no. 12, pp. 2280-2285. https://doi.org/10.1002/mds.30003

TY - JOUR

T1 - Effect of GBA1 Mutations and APOE Polymorphisms on Survival and Progression Among Ashkenazi Jews with Dementia with Lewy Bodies

AU - Shiner, Tamara

AU - Kavé, Gitit

AU - Mirelman, Anat

AU - Regev, Keren

AU - Piura, Yoav

AU - Goldstein, Orly

AU - Gana Weisz, Mali

AU - Bar-Shira, Anat

AU - Gurevich, Tanya

AU - Orr-Urtreger, Avi

AU - Alcalay, Roy N

AU - Giladi, Nir

AU - Bregman, Noa

PY - 2024/12

Y1 - 2024/12

N2 - BACKGROUND: Glucocerebrosidase 1 (GBA1) mutations are associated with reduced survival in Parkinson's disease but their effect on survival in dementia with Lewy bodies (DLB) is unclear.OBJECTIVE: To assess the impact of GBA1 mutations on survival among Ashkenazi Jews with DLB, while controlling for APOE status.METHODS: One hundred and forty participants from Tel Aviv Medical Center, Israel were genotyped for GBA1 mutations and APOE polymorphisms. Survival rates and follow-up cognitive screening scores were analyzed.RESULTS: GBA1 mutation carriers had a two-fold increased risk of death (HR = 1.999), while APOE status did not independently affect survival. In a subset of patients with available clinical data (N = 63), carriers of the APOE ε4 allele showed faster cognitive deterioration, while GBA1 mutation carriers also declined more rapidly albeit not significantly.CONCLUSION: Understanding the genetic effects on survival and progression is crucial for patient counseling and inclusion in clinical trials.

AB - BACKGROUND: Glucocerebrosidase 1 (GBA1) mutations are associated with reduced survival in Parkinson's disease but their effect on survival in dementia with Lewy bodies (DLB) is unclear.OBJECTIVE: To assess the impact of GBA1 mutations on survival among Ashkenazi Jews with DLB, while controlling for APOE status.METHODS: One hundred and forty participants from Tel Aviv Medical Center, Israel were genotyped for GBA1 mutations and APOE polymorphisms. Survival rates and follow-up cognitive screening scores were analyzed.RESULTS: GBA1 mutation carriers had a two-fold increased risk of death (HR = 1.999), while APOE status did not independently affect survival. In a subset of patients with available clinical data (N = 63), carriers of the APOE ε4 allele showed faster cognitive deterioration, while GBA1 mutation carriers also declined more rapidly albeit not significantly.CONCLUSION: Understanding the genetic effects on survival and progression is crucial for patient counseling and inclusion in clinical trials.

KW - Aged

KW - Aged, 80 and over

KW - Apolipoproteins E/genetics

KW - Disease Progression

KW - Female

KW - Genotype

KW - Glucosylceramidase/genetics

KW - Humans

KW - Israel

KW - Jews/genetics

KW - Lewy Body Disease/genetics

KW - Male

KW - Middle Aged

KW - Mutation/genetics

KW - Polymorphism, Genetic/genetics

U2 - 10.1002/mds.30003

DO - 10.1002/mds.30003

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C2 - 39212252

SN - 0885-3185

VL - 39

SP - 2280

EP - 2285

JO - Movement Disorders

JF - Movement Disorders

IS - 12

ER -

Effect of GBA1 Mutations and APOE Polymorphisms on Survival and Progression Among Ashkenazi Jews with Dementia with Lewy Bodies

Abstract

Bibliographical note

Keywords

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