In neurological disorders, such as Alzheimer's disease, temporal lobe epilepsy and cerebral trauma, the presence of the apolipoprotein E (ApoE) allele epsilon4 is associated with an increased vulnerability of the brain to the effects of the disease, whereas the presence of the ApoE genotype epsilon3/3 appears to provide moderate neuroprotection.
To investigate the difference in the morphologic expression of frontotemporal dementia (FTD) and Alzheimer's disease (AD) in patients carrying and not carrying the epsilon4 allele of APOE, MR images of 26 controls, 18 AD patients (11 carrying the epsilon4 allele, seven non-carriers), and eight FTD (two carriers, six non-carriers) were compared using voxel by voxel analysis.
Among 34 cholesterol-related genes for which association with AD has been described APOE, CH25H, CLU, LDLR, SORL1 outstand with positive meta-analyses.
Peptide Ac-hE18A-NH2 attenuates the effects of oxidative stress on ApoE secretion, inhibits amyloid plaque deposition, and thus could be beneficial in the treatment of Alzheimer's disease.
Other clinical variables included white matter lesion (WML) and intracranial brain (ICV) volumes derived from magnetic resonance imaging, ratings of overall cognitive function (Alzheimer's Disease Assessment Scale, ADAS), and apolipoprotein E (ApoE) status.
Apolipoprotein E (apoE) has an important role in the pathogenesis of Alzheimer's disease with its three isoforms having distinct effects on disease risk.
In Western societies the apolipoprotein E4 (apoE4) genotype is associated with increased morbidity and mortality and represents a significant risk factor for cardiovascular and Alzheimer's disease.
We hypothesize that APOE4 influences all the pathological hallmarks of AD and may sit at the interface between neurodegeneration, inflammation and the spread of pathologies through the brain.
In survival analyses, age (hazard ratio [HR] 1.04, 95% 1.03-1.05), baseline Mini-Mental State Exam (HR 0.85, 95% confidence interval 0.83-0.87), amnestic subtype of mild cognitive impairment (HR 1.66, 95% 1.30-2.12), presence of APOE4 allele (HR 1.99, 1.69-2.36), and presence of active depression within the last two years (HR 1.44, 95% confidence interval 1.16-1.79) were all independently associated with increased risk of Alzheimer dementia.
An early temporo-parietal interhemispheric asymmetry might cause a pathological spatial bias which is associated with ApoE4 genotype and may therefore function as early cognitive marker of upcoming AD.
Brain regions showing a significant APOE epsilon4 allele load effect on GMV in AD included only some of those typically described as having greatest amyloid plaque deposition and atrophy.
Furthermore, recent identification of a low frequency mutation in the gene encoding the triggering receptor expressed in myeloid cells 2 protein (TREM2) confers increased risk of AD in LOAD cohorts with an effect size similar to that for APOE, until recently the only identified genetic risk factor associated with LOAD [9,10(••)] (Figure 1).
The findings also suggest that cross-modal ERP studies of recognition memory discriminate early neurocognitive changes in ApoE epsilon4(+) and ApoE epsilon4(-) individuals and may contribute to identifying the phenotype of persons who will develop Alzheimer's disease.