Tract-specific differences in white matter microstructure between young adult APOE ε4 carriers and non-carriers: A replication and extension study

Lissaman, Rikki; Lancaster, Thomas M.; Parker, Greg D.; Graham, Kim S.; Lawrence, Andrew David; Hodgetts, Carl J.

doi:10.1016/j.ynirp.2022.100126

Cited by 4 publications

(4 citation statements)

References 127 publications

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“…Specifically, several studies have had similar null findings. Most recently, Lissaman et al reported no significant differences in white or grey matter between healthy younger APOE-ε4 carriers and non-carriers, in line with the current study and previous work suggesting no differences in GMV between carriers and non-carriers of the ε4 allele [38][39][40]. Studies that have taken a longitudinal approach have also suggested that the presence of APOE-ε4 does not affect the rate of GMV change over time in the hippocampal or thalamic PLOS ONE regions [22].…”

Section: Discussionsupporting

confidence: 92%

Impact of APOE-ε alleles on brain structure and cognitive function in healthy older adults: A VBM and DTI replication study

Lacey,

Paterson,

Gawryluk

2024

PLoS ONE

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Background The Apolipoprotein E (APOE) gene has been established in the Alzheimer’s disease (AD) literature to impact brain structure and function and may also show congruent effects in healthy older adults, although findings in this population are much less consistent. The current study aimed to replicate and expand the multimodal approach employed by Honea et al. Structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and neuropsychological measures were used to investigate the impact of APOE-ε status on grey matter structure, white matter integrity, and cognitive functioning. Methods Data were obtained from the Alzheimer’s Disease Initiative Phase 3 (ADNI3) database. Baseline MRI, DTI and cognitive composite scores for memory (ADNI-Mem) and executive function (ADNI-EF) were acquired from 116 healthy controls. Participants were grouped according to APOE allele presence (APOE-ε2+ N = 17, APOE-ε3ε3 N = 64, APOE-ε4+ N = 35). Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to compare grey matter volume (GMV) and white matter integrity, respectively, between APOE-ε2+ and APOE-ε3ε3 controls, and again between APOE-ε4+ and APOE-ε3ε3 controls. Multivariate analysis of covariance (MANCOVA) was used to examine the effects of APOE polymorphism on memory and EF across all APOE groups with age, sex and education as regressors of no interest. Cognitive scores were correlated (Pearson r) with imaging metrics within groups. Results No significant differences were seen across groups, within groups in MRI metrics, or cognitive performance (p>0.05, corrected for multiple comparisons). Conclusions The current study partially replicated and extended previous findings from an earlier multimodal study (Honea 2009). Future studies should clarify APOE mechanisms in healthy ageing by adding other imaging, cognitive, and lifestyle metrics and longitudinal design in larger sample sizes.

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Section: Discussionsupporting

confidence: 92%

Impact of APOE-ε alleles on brain structure and cognitive function in healthy older adults: A VBM and DTI replication study

Lacey,

Paterson,

Gawryluk

2024

PLoS ONE

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“…Hodgetts et al reported an unexpected pattern of higher FA and lower MD in the PHCB of healthy young ε4 carriers aged 18 to 26 years, suggesting that this hyper-connectivity may increase vulnerability to amyloid-β accumulation and/or tau spread in later life 55 . However, a recent study by Lissaman et al replicated Hodgetts et al's findings but failed to find statistically significant effects in the expected direction and even provided evidence against their presence 56 . Possible explanations for the discrepancy include false positives in Hodgetts et al's study or an exaggerated effect size due to a small sample size (15/100 subjects).…”

Section: Effects Of Ad Genetic Risk Factors On Brain Structure and Fu...mentioning

confidence: 86%

Impact of genetic predisposition to late-onset neurodegenerative diseases on early life outcomes and brain structure

Ogonowski,

García-Marín,

Fernando

et al. 2023

Preprint

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Most patients with late-onset neurodegenerative diseases such as Alzheimer's and Parkinson's have a complex aetiology resulting from numerous genetic risk variants of small effects located across the genome, environmental factors, and the interaction between genes and environment. Over the last decade, genome-wide association studies (GWAS) and post-GWAS analyses have shed light on the polygenic architecture of these diseases, enabling the use of polygenic risk scores (PRS) for estimating an individual's relative genetic liability for presenting with the disease. PRS can screen and stratify individuals based on their genetic risk, potentially years or even decades before the onset of clinical symptoms. An emerging body of evidence from various research studies suggests that genetic susceptibility to late-onset neurodegenerative diseases might impact early life outcomes, including cognitive function, brain structure and function, and behaviour. This article summarises recent findings exploring the potential impact of genetic susceptibility to neurodegenerative diseases on early life outcomes. A better understanding of the impact of genetic susceptibility to neurodegenerative diseases early in life could be valuable in disease screening, detection, and prevention and inform treatment strategies before significant neural damage has occurred. However, ongoing studies have limitations. Overall, our review found several studies focused on APOE haplotypes and Alzheimer's risk, but a limited number of studies leveraging polygenic risk scores or focused on genetic susceptibility to other late-onset conditions.

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“…Hodgetts et al reported an unexpected pattern of higher FA and lower MD in the PHCB of healthy young ε4 carriers aged 18-26 years, suggesting that this hyper-connectivity may increase vulnerability to amyloid-β accumulation and/or tau spread in later life [55]. However, a recent study by Lissaman et al replicated Hodgetts et al's findings but failed to find statistically significant effects in the expected direction and even provided evidence against their presence [56]. Possible explanations for the discrepancy include false positives in Hodgetts et al's study or an exaggerated effect size due to a small sample size (15/ 100 subjects).…”

Section: Alzheimer's Diseasementioning

confidence: 94%

Impact of genetic predisposition to late-onset neurodegenerative diseases on early life outcomes and brain structure

Ogonowski,

García-Marín,

Fernando

et al. 2024

Transl Psychiatry

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Most patients with late-onset neurodegenerative diseases such as Alzheimer’s and Parkinson’s have a complex aetiology resulting from numerous genetic risk variants of small effects located across the genome, environmental factors, and the interaction between genes and environment. Over the last decade, genome-wide association studies (GWAS) and post-GWAS analyses have shed light on the polygenic architecture of these diseases, enabling polygenic risk scores (PRS) to estimate an individual’s relative genetic liability for presenting with the disease. PRS can screen and stratify individuals based on their genetic risk, potentially years or even decades before the onset of clinical symptoms. An emerging body of evidence from various research studies suggests that genetic susceptibility to late-onset neurodegenerative diseases might impact early life outcomes, including cognitive function, brain structure and function, and behaviour. This article summarises recent findings exploring the potential impact of genetic susceptibility to neurodegenerative diseases on early life outcomes. A better understanding of the impact of genetic susceptibility to neurodegenerative diseases early in life could be valuable in disease screening, detection, and prevention and in informing treatment strategies before significant neural damage has occurred. However, ongoing studies have limitations. Overall, our review found several studies focused on APOE haplotypes and Alzheimer’s risk, but a limited number of studies leveraging polygenic risk scores or focused on genetic susceptibility to other late-onset conditions.

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Tract-specific differences in white matter microstructure between young adult APOE ε4 carriers and non-carriers: A replication and extension study

Cited by 4 publications

References 127 publications

Impact of APOE-ε alleles on brain structure and cognitive function in healthy older adults: A VBM and DTI replication study

Impact of APOE-ε alleles on brain structure and cognitive function in healthy older adults: A VBM and DTI replication study

Impact of genetic predisposition to late-onset neurodegenerative diseases on early life outcomes and brain structure

Impact of genetic predisposition to late-onset neurodegenerative diseases on early life outcomes and brain structure

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