The effects of APOE-ε4 on the BOLD response

Trachtenberg, Aaron J.; Filippini, Nicola; Mackay, Clare E.

doi:10.1016/j.neurobiolaging.2010.03.009

Cited by 90 publications

(81 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because the DMN correlate negatively with task-related networks , increased hippocampal activity during rest might decrease hippocampal activation relative to baseline during memory tasks, explaining an apparent deficiency in memoryrelated hippocampal activation (Fleisher et al, 2009b). However, further studies delineating APOE effects on the functional interactions between task and rest are needed (Trachtenberg et al, 2010). Also, longitudinal studies are warranted to determine whether increased DMN synchronization is associated with higher risk of pathological brain and cognitive changes at a later stage.…”

Section: Discussionmentioning

confidence: 99%

Increased Hippocampal Default Mode Synchronization during Rest in Middle-Aged and Elderly APOE ε4 Carriers: Relationships with Memory Performance

Westlye

Lundervold²,

Rootwelt³

et al. 2011

J. Neurosci.

164

130

View full text Add to dashboard Cite

The apolipoprotein (APOE) 4 allele is a strong genetic risk factor for Alzheimer's disease (AD). Intrinsic fluctuations of brain activity measured by fMRI during rest may be sensitive to AD-related neuropathology. In particular, functional connectivity of the default-mode network (DMN) has gained recent attention as a possible biomarker of disease processes and associated memory decline in AD. Here, we tested the hypothesis of APOE-related alterations in DMN functional connectivity in 95 healthy individuals between 50 and 80 years of age, including 33 carriers of the 4 allele. Based on previous studies, we hypothesized increased hippocampal DMN synchronization in APOE 4 carriers. This was supported using independent component analysis in combination with a dual-regression approach for analysis of resting state data. Whole-brain analysis suggested effects also in other areas, including the posterior cingulate cortex, parietal cortex, and parahippocampal regions. DMN synchronization showed a negative correlation with performance on a test of memory functioning, suggesting a neurocognitive significance of the brain activity patterns during rest. Our findings indicate that increased genetic vulnerability for AD is reflected in increased hippocampal DMN synchronization during rest several years before clinical manifestation. We propose that the results reflect 4-related failure in hippocampal decoupling, which might elevate the total hippocampal metabolic burden and increase the risk of cognitive decline and AD. The results provide an important confirmation of specific genotype effects on intrinsic fluctuations and support the use of functional connectivity indices as imaging-derived endophenotypes in the emerging field of imaging genetics.

show abstract

Section: Discussionmentioning

confidence: 99%

Increased Hippocampal Default Mode Synchronization during Rest in Middle-Aged and Elderly APOE ε4 Carriers: Relationships with Memory Performance

Westlye

Lundervold²,

Rootwelt³

et al. 2011

J. Neurosci.

164

130

View full text Add to dashboard Cite

show abstract

“…26,27 Neural activity alteration in WM in subjects at risk of AD is not conclusive. 28 An initial study by Burggren et al 29 by using a digit-span task showed no difference in activation patterns between elderly APOE4 carriers and non-APOE4 carriers. They concluded that additional cognitive effort in persons at genetic risk for AD is specific to episodic encoding.…”

mentioning

confidence: 97%

Effects of theApolipoprotein Eε4 Allele on Functional MRI duringn-Back Working Memory Tasks in Healthy Middle-Aged Adults

Chen¹,

Chen

et al. 2012

AJNR Am J Neuroradiol

View full text Add to dashboard Cite

BACKGROUND AND PURPOSE:APOE4 is the best-documented genetic risk factor for sporadic AD. Previous research showed that APOE4 is associated with increased risk of occurrence and earlier onset of AD in a gene dose-dependent manner. However, the specific role of APOE4 in processing of brain functions requires further investigation. Investigators have used fMRI to measure brain activity on the basis of the blood oxygen level-dependent contrast. This study investigates the effects of APOE4 on fMRI during n-back WM tasks in healthy middle-aged adults.

show abstract

“…Although this pattern may be partially seen as the result of compensatory mechanisms (especially with regard to the increased connectivity seen in the frontal lobe), there are two interpretational avenues that identify these differences as maladaptive. First the "hyperfunctional hippocampus" hypothesis suggests that the excessive seed-to-parietal connectivity might be dysfunctional as negatively associated with cognitive performance [48][49]. This eventuality was ruled out by post-hoc analyses, which confirmed that the magnitude of connectivity along this pathway was positively associated with memory performance (characterising it as compensatory).…”

Section: Resultsmentioning

confidence: 93%

“…This was accounted for by the hypothesis of compensatory mechanisms taking over from the AD-dependent disruption of "standard" patterns of connectivity. The idea that a functional reorganisation of regional connectivity occurs in healthy adults with a risk factor for AD is also supported by studies of taskassociated fMRI, in which evidence of computational differences has been repeatedly reported, albeit with no constant pattern [49]. Our results suggest that compensatory mechanisms may be triggered in 4 carriers even after the possible onset of neurodegeneration, or it might be the outcome of the brain over-time coping with the subtle negative effects of this genetic risk factor.…”

Section: Discussionmentioning

confidence: 90%

ApoE ε4 Allele Related Alterations in Hippocampal Connectivity in Early Alzheimer’s Disease Support Memory Performance

Marco

Vallelunga

Meneghello

et al. 2017

CAR

View full text Add to dashboard Cite

The effects of APOE-ε4 on the BOLD response

Cited by 90 publications

References 48 publications

Increased Hippocampal Default Mode Synchronization during Rest in Middle-Aged and Elderly APOE ε4 Carriers: Relationships with Memory Performance

Increased Hippocampal Default Mode Synchronization during Rest in Middle-Aged and Elderly APOE ε4 Carriers: Relationships with Memory Performance

Effects of theApolipoprotein Eε4 Allele on Functional MRI duringn-Back Working Memory Tasks in Healthy Middle-Aged Adults

ApoE ε4 Allele Related Alterations in Hippocampal Connectivity in Early Alzheimer’s Disease Support Memory Performance

Contact Info

Product

Resources

About