Six genetically linked mutations in the CD36 gene significantly
delay the onset of Alzheimer's disease

J 2022

Six genetically linked mutations in the CD36 gene significantly delay the onset of Alzheimer's disease

ŠERÝ, Omar, Tomáš ZEMAN, Kateřina SHEARDOVÁ, Martin VYHNÁLEK, Hana MARKOVÁ et. al.

Základní údaje

Originální název

Six genetically linked mutations in the CD36 gene significantly delay the onset of Alzheimer's disease

Autoři

ŠERÝ, Omar (203 Česká republika, garant, domácí), Tomáš ZEMAN (203 Česká republika, domácí), Kateřina SHEARDOVÁ (203 Česká republika), Martin VYHNÁLEK (203 Česká republika), Hana MARKOVÁ (203 Česká republika), Jan LACZÓ, Jan LOCHMAN (203 Česká republika, domácí), Petr KRÁLÍK (203 Česká republika), Kamila VRZALOVÁ (203 Česká republika, domácí), Radka DZIEDZINSKÁ (203 Česká republika), Vladimír Josef BALCAR (36 Austrálie) a Jakub HORT

Vydání

Scientific Reports, Nature Research, 2022, 2045-2322

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30210 Clinical neurology

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.600

Kód RIV

RIV/00216224:14310/22:00127724

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1038/s41598-022-15299-z

UT WoS

000818983300016

Klíčová slova anglicky

Alzheimer’s disease; CD36; gene; polymorphism; ApoE

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 13. 3. 2023 09:23, prof. RNDr. Omar Šerý, Ph.D.

Anotace

V originále

The risk of Alzheimer’s disease (AD) has a strong genetic component, also in the case of late-onset AD (LOAD). Attempts to sequence whole genome in large populations of subjects have identified only a few mutations common to most of the patients with AD. Targeting smaller well-characterized groups of subjects where specific genetic variations in selected genes could be related to precisely defined psychological traits typical of dementia is needed to better understand the heritability of AD. More than one thousand participants, categorized according to cognitive deficits, were assessed using 14 psychometric tests evaluating performance in five cognitive domains (attention/working memory, memory, language, executive functions, visuospatial functions). CD36 was selected as a gene previously shown to be implicated in the etiology of AD. A total of 174 polymorphisms were tested for associations with cognition-related traits and other AD-relevant data using the next generation sequencing. Several associations between single nucleotide polymorphisms (SNP’s) and the cognitive deficits have been found (rs12667404 with language performance, rs3211827 and rs41272372 with executive functions, rs137984792 with visuospatial performance). The most prominent association was found between a group of genotypes in six genetically linked and the age at which the AD patients presented with, or developed, a full-blown dementia. The identified alleles appear to be associated with a delay in the onset of LOAD. In silico studies suggested that the SNP’s alter the expression of CD36 thus potentially affecting CD36-related neuroinflammation and other molecular and cellular mechanisms known to be involved in the neuronal loss leading to AD. The main outcome of the study is an identification of a set of six new mutations apparently conferring a distinct protection against AD and delaying the onset by about 8 years. Additional mutations in CD36 associated with certain traits characteristic of the cognitive decline in AD have also been found.

Citovat

ŠERÝ, Omar, Tomáš ZEMAN, Kateřina SHEARDOVÁ, Martin VYHNÁLEK, Hana MARKOVÁ, Jan LACZÓ, Jan LOCHMAN, Petr KRÁLÍK, Kamila VRZALOVÁ, Radka DZIEDZINSKÁ, Vladimír Josef BALCAR a Jakub HORT. Six genetically linked mutations in the CD36 gene significantly delay the onset of Alzheimer's disease. Scientific Reports. Nature Research, 2022, roč. 12, č. 1, s. 1-16. ISSN 2045-2322. Dostupné z: https://dx.doi.org/10.1038/s41598-022-15299-z.

@article{2243759,
   author = {Šerý, Omar and Zeman, Tomáš and Sheardová, Kateřina and Vyhnálek, Martin and Marková, Hana and Laczó, Jan and Lochman, Jan and Králík, Petr and Vrzalová, Kamila and Dziedzinská, Radka and Balcar, Vladimír Josef and Hort, Jakub},
   article_number = {1},
   doi = {http://dx.doi.org/10.1038/s41598-022-15299-z},
   keywords = {Alzheimer’s disease; CD36; gene; polymorphism; ApoE},
   language = {eng},
   issn = {2045-2322},
   journal = {Scientific Reports},
   title = {Six genetically linked mutations in the CD36 gene significantly delay the onset of Alzheimer's disease},
   url = {https://www.nature.com/articles/s41598-022-15299-z},
   volume = {12},
   year = {2022}
}

TY  - JOUR
ID  - 2243759
AU  - Šerý, Omar - Zeman, Tomáš - Sheardová, Kateřina - Vyhnálek, Martin - Marková, Hana - Laczó, Jan - Lochman, Jan - Králík, Petr - Vrzalová, Kamila - Dziedzinská, Radka - Balcar, Vladimír Josef - Hort, Jakub
PY  - 2022
TI  - Six genetically linked mutations in the CD36 gene significantly delay the onset of Alzheimer's disease
JF  - Scientific Reports
VL  - 12
IS  - 1
SP  - 1-16
EP  - 1-16
PB  - Nature Research
SN  - 20452322
KW  - Alzheimer’s disease
KW  - CD36
KW  - gene
KW  - polymorphism
KW  - ApoE
UR  - https://www.nature.com/articles/s41598-022-15299-z
N2  - The risk of Alzheimer’s disease (AD) has a strong genetic component, also in the case of late-onset AD (LOAD). Attempts to sequence whole genome in large populations of subjects have identified only a few mutations common to most of the patients with AD. Targeting smaller well-characterized groups of subjects where specific genetic variations in selected genes could be related to precisely defined psychological traits typical of dementia is needed to better understand the heritability of AD. More than one thousand participants, categorized according to cognitive deficits, were assessed using 14 psychometric tests evaluating performance in five cognitive domains (attention/working memory, memory, language, executive functions, visuospatial functions). CD36 was selected as a gene previously shown to be implicated in the etiology of AD. A total of 174 polymorphisms were tested for associations with cognition-related traits and other AD-relevant data using the next generation sequencing. Several associations between single nucleotide polymorphisms (SNP’s) and the cognitive deficits have been found (rs12667404 with language performance, rs3211827 and rs41272372 with executive functions, rs137984792 with visuospatial performance). The most prominent association was found between a group of genotypes in six genetically linked and the age at which the AD patients presented with, or developed, a full-blown dementia. The identified alleles appear to be associated with a delay in the onset of LOAD. In silico studies suggested that the SNP’s alter the expression of CD36 thus potentially affecting CD36-related neuroinflammation and other molecular and cellular mechanisms known to be involved in the neuronal loss leading to AD. The main outcome of the study is an identification of a set of six new mutations apparently conferring a distinct protection against AD and delaying the onset by about 8 years. Additional mutations in CD36 associated with certain traits characteristic of the cognitive decline in AD have also been found.
ER  -

ŠERÝ, Omar, Tomáš ZEMAN, Kateřina SHEARDOVÁ, Martin VYHNÁLEK, Hana MARKOVÁ, Jan LACZÓ, Jan LOCHMAN, Petr KRÁLÍK, Kamila VRZALOVÁ, Radka DZIEDZINSKÁ, Vladimír Josef BALCAR a Jakub HORT. Six genetically linked mutations in the CD36 gene significantly delay the onset of Alzheimer's disease. \textit{Scientific Reports}. Nature Research, 2022, roč.~12, č.~1, s.~1-16. ISSN~2045-2322. Dostupné z: https://dx.doi.org/10.1038/s41598-022-15299-z.

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