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

@article{b41bbac4269946df8b1d0935441dde61,

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

UR - https://www.scopus.com/pages/publications/85202875545

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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