Associations between APOE genotype and cerebral small-vessel disease: a longitudinal study

Abstract

ObjectiveIt remains unclear if and how the interactions between APOE genotypes and cerebral small-vessel diseases (CSVD) lead to cognitive decline in the long term. Based on ADNI cohort, this longitudinal study aimed to clarify the potential relationship among APOE genotype, CSVD and cognition by integrating multi-level data.MethodThere were 135 healthy elderly (including ε2, ε4 allele carriers and ε3 homozygotes) who had completed two years’ follow-up. MRI markers of CSVD, including white matter hyperintensities (WMH), dilated perivascular space (dPVS), microbleeds and lacune, were assessed. Besides, neuropathological factors including Alzheimer's disease-related pathology measured by CSF and PiB-PET were assessed. Repeated measurements ANOVAs were performed to test impact of different APOE genotypes on CSVD.ResultsWe found that APOE ε4 carriers had significantly more frontal WMH burden and basal ganglia dPVS at baseline and faster progression of frontal WMH burden during follow-up. Furthermore, our results showed that APOE ε4 carriers had significantly decreased Aβ1-42 level, and its level was negatively related with baseline and progressive total WMH burden. Then, general linear modals indicated interaction between basal frontal WMH burden and ε4 allele was related with declining trend of cognition.ConclusionOur findings suggested APOE ε4 allele was associated with increased Aβ deposition, which may lead to the formation and progression of WMH, especially in frontal lobe. Besides, interaction between the increased frontal WMH burden and ε4 allele can exert long-term detrimental effects on individual's trajectory of cognition.

Apoe Genotypes and Cerebral Microbleeds on Mri in Han Chinese Population

“…Previous findings suggested APOE ε4 allele was associated with increased Aβ deposition, which may lead to the formation and progression of WMH, especially in frontal lobe [12]. There are significant relationships between CMBs with Aβ load [13].This can not explain why the ε2 allele, not ε4 allele is closely related to lobar CMBs which has been obtained in the present study. It is speculated that there may be some other mechanism related to APOE ε2, which is involved in the occurrence of CMBs.…”

“…High-quality meta-analytic report (24 studies, n=8546) recommended that there was no association between APOE ε4 allele and WMH [4]. And another metaanalysis (11 studies, n=8917) suggested that APOE ε4 allele carrier significantly associated with increased WMH and CMBs, and APOE ε2 alleles carrier was significantly related with increasing WMH load [5] [6]. This suggests that racial differences can not only induce differences in CMBs frequency and distribution but also differences in their association with APOE genotypes [7,8].…”

APOE ε4, white matter hyperintensities, and cognition in Alzheimer and Lewy body dementia

“…41 Faster WMH progression rates were noted in APOE e4-positive patients with AD and healthy adults, supporting our interaction hypothesis. 38,42 APOE e4 carriers might also have more covert white matter damage that is not detected by routine imaging, 43 but is reflected as worse cognitive outcomes. Future large prospective studies are needed.…”

Decreased Bilateral FDG-PET Uptake and Inter-Hemispheric Connectivity in Multi-Domain Amnestic Mild Cognitive Impairment Patients: A Preliminary Study

“…Coincidentally, their work also found that reduced PCu activity was related to worse executive ability ( Li et al, 2014 ). As a central role in the primary executive networks, studies of the AD and MCI frequently reported that regional PCu deficit associated with the decreased executive ability ( Sridharan et al, 2008 ; Chen et al, 2013 ; Luo et al, 2017a , b ). Furthermore, we found that left PCu hypometabolism was related to amyloid deposition.…”