APOE genotype and neuroimaging markers of Alzheimer's disease: systematic review and meta-analysis

Liu, Ying; Yu, Jin‐Tai; Wang, Hui Fu; Han, Pei Ran; Tan, Chen Chen; Wang, Chong; Meng, Xiang Fei; Risacher, Shannon L.; Saykin, Andrew J.; Tan, Lan

doi:10.1136/jnnp-2014-307719

Cited by 128 publications

(102 citation statements)

References 40 publications

(50 reference statements)

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“…The APOE e4 allele has been shown to increase risk for developing AD in both the DS (Coppus et al, 2008;Prasher et al, 2008;Rohn et al, 2014) and TD populations (Bertram and Tanzi, 2008;Corder et al, 1993;Liu et al, 2015). The observed e4 carrier frequency was 5 out of 54 alleles, or 9%, which is similar to the frequency observed in the general population (13%) (Bertram and Tanzi, 2008;Corder et al, 1993;Liu et al, 2015).…”

Section: Exploratory Analyses In Dsmentioning

confidence: 54%

Resting-State Functional Connectivity in Individuals with Down Syndrome and Williams Syndrome Compared with Typically Developing Controls

et al. 2015

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The emergence of resting-state functional connectivity (rsFC) analysis, which examines temporal correlations of low-frequency ( < 0.1 Hz) blood oxygen level-dependent signal fluctuations between brain regions, has dramatically improved our understanding of the functional architecture of the typically developing (TD) human brain. This study examined rsFC in Down syndrome (DS) compared with another neurodevelopmental disorder, Williams syndrome (WS), and TD. Ten subjects with DS, 18 subjects with WS, and 40 subjects with TD each participated in a 3-Tesla MRI scan. We tested for group differences (DS vs. TD, DS vs. WS, and WS vs. TD) in between-and within-network rsFC connectivity for seven functional networks. For the DS group, we also examined associations between rsFC and other cognitive and genetic risk factors. In DS compared with TD, we observed higher levels of between-network connectivity in 6 out 21 network pairs but no differences in within-network connectivity. Participants with WS showed lower levels of within-network connectivity and no significant differences in between-network connectivity relative to DS. Finally, our comparison between WS and TD controls revealed lower within-network connectivity in multiple networks and higher betweennetwork connectivity in one network pair relative to TD controls. While preliminary due to modest sample sizes, our findings suggest a global difference in between-network connectivity in individuals with neurodevelopmental disorders compared with controls and that such a difference is exacerbated across many brain regions in DS. However, this alteration in DS does not appear to extend to within-network connections, and therefore, the altered between-network connectivity must be interpreted within the framework of an intact intra-network pattern of activity. In contrast, WS shows markedly lower levels of within-network connectivity in the default mode network and somatomotor network relative to controls. These findings warrant further investigation using a taskbased procedure that may help disentangle the relationship between brain function and cognitive performance across the spectrum of neurodevelopmental disorders.

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Section: Exploratory Analyses In Dsmentioning

confidence: 54%

Resting-State Functional Connectivity in Individuals with Down Syndrome and Williams Syndrome Compared with Typically Developing Controls

et al. 2015

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“…However, this study described higher baseline CBF in ApoE4 carriers at baseline, which we only observed in the anterior cingulate cortex. A recent meta-analysis 48 identified the right middle frontal gyrus, the region which is most consistently identified to be hypometabolic in FDG-PET studies. This region also showed reduced CBF in our analysis.…”

Section: Influence Of Apoe and Pib On Cbfmentioning

confidence: 99%

Arterial spin labeling imaging reveals widespread and Aβ-independent reductions in cerebral blood flow in elderly apolipoprotein epsilon-4 carriers

Michels

Warnock

Buck

et al. 2015

J Cereb Blood Flow Metab

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Changes in cerebral blood flow are an essential feature of Alzheimer's disease and have been linked to apolipoprotein E-genotype and cerebral amyloid-deposition. These factors could be interdependent or influence cerebral blood flow via different mechanisms. We examined apolipoprotein E-genotype, amyloid beta-deposition, and cerebral blood flow in amnestic mild cognitive impairment using pseudo-continuous arterial spin labeling MRI in 27 cognitively normal elderly and 16 amnestic mild cognitive impairment participants. Subjects underwent Pittsburgh Compound B (PiB) positron emission tomography and apolipoprotein E-genotyping. Global cerebral blood flow was lower in apolipoprotein E "4-allele carriers (apolipoprotein E4þ) than in apolipoprotein E4À across all subjects (including cognitively normal participants) and within the group of cognitively normal elderly. Global cerebral blood flow was lower in subjects with mild cognitive impairment compared with cognitively normal. Subjects with elevated cerebral amyloid-deposition (PiBþ) showed a trend for lower global cerebral blood flow. Apolipoprotein E-status exerted the strongest effect on global cerebral blood flow. Regional analysis indicated that local cerebral blood flow reductions were more widespread for the contrasts apolipoprotein E4þ versus apolipoprotein E4À compared with the contrasts PiBþ versus PiBÀ or mild cognitive impairment versus cognitively normal. These findings suggest that apolipoprotein E-genotype exerts its impact on cerebral blood flow at least partly independently from amyloid beta-deposition, suggesting that apolipoprotein E also contributes to cerebral blood flow changes outside the context of Alzheimer's disease.

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“…[1][2][3] The inverse relationship between fibrillar b-amyloid plaque load and regional glucose metabolism is particularly intriguing, [4][5][6] and recent studies have interrogated the complex relationship between b-amyloid, metabolism, and genotype.…”

Section: Introductionmentioning

confidence: 99%

Modulation of glucose metabolism and metabolic connectivity by β-amyloid

Carbonell

Zijdenbos

McLaren

et al. 2016

J Cereb Blood Flow Metab

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Glucose hypometabolism in the pre-clinical stage of Alzheimer's disease (AD) has been primarily associated with the APOE e4 genotype, rather than fibrillar b-amyloid. In contrast, aberrant patterns of metabolic connectivity are more strongly related to b-amyloid burden than APOE e4 status. A major limitation of previous studies has been the dichotomous classification of subjects as amyloid-positive or amyloid-negative. Dichotomous treatment of a continuous variable, such as b-amyloid, potentially obscures the true relationship with metabolism and reduces the power to detect significant changes in connectivity. In the present work, we assessed alterations of glucose metabolism and metabolic connectivity as continuous function of b-amyloid burden using positron emission tomography scans from the Alzheimer's Disease Neuroimaging Initiative study. Modeling b-amyloid as a continuous variable resulted in better model fits and improved power compared to the dichotomous model. Using this continuous model, we found that both APOE e4 genotype and b-amyloid burden are strongly associated with glucose hypometabolism at early stages of Alzheimer's disease. We also determined that the cumulative effects of b-amyloid deposition result in a particular pattern of altered metabolic connectivity, which is characterized by global, synchronized hypometabolism at early stages of the disease process, followed by regionally heterogeneous, progressive hypometabolism.

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APOE genotype and neuroimaging markers of Alzheimer's disease: systematic review and meta-analysis

Cited by 128 publications

References 40 publications

Resting-State Functional Connectivity in Individuals with Down Syndrome and Williams Syndrome Compared with Typically Developing Controls

Resting-State Functional Connectivity in Individuals with Down Syndrome and Williams Syndrome Compared with Typically Developing Controls

Arterial spin labeling imaging reveals widespread and Aβ-independent reductions in cerebral blood flow in elderly apolipoprotein epsilon-4 carriers

Modulation of glucose metabolism and metabolic connectivity by β-amyloid

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