Effect of apolipoprotein E on biomarkers of amyloid load and neuronal pathology in Alzheimer disease.

摘要: Apolipoprotein E (APOE) e4 is the most important known genetic risk factor for typical late onset Alzheimer disease (AD). The lifetime of developing AD increased and age lowered with increasing number APOE alleles.1–4 Aβ1–42 tau levels measured in cerebrospinal fluid (CSF) atrophy seen on magnetic resonance imaging (MRI) are indicators disease-related pathological processes AD. Low CSF reflects deposition Aβ plaques.5 High t-tau reflect active axonal neuronal damage.6 Atrophy MRI direct result loss neurons, synapses, dendritic arborization.7 In this paper, we use Structural Abnormality Index (STAND) scores as an indicator severity AD-like pattern structural MRI. STAND were developed our lab to condense location AD-related 3-dimensional scan into a single number.8 The effect genotype pathology amyloid load has been studied autopsy specimens.9–13 Several vivo studies,14–17 studies,18–22 fluorodeoxyglucose-positron emission tomography (PET) studies23–25 have also independently each these modalities. first Alzheimer's Disease Neuroimaging Initiative (ADNI) biomarker study investigated biomarkers, found that concentration lowest subjects 2 alleles rises decreases.26 However, there not studies influence allele surrogates together by cohort spans cognitive spectrum. The main aim paper was evaluate biomarkers answering questions: (1) How does within clinical group? (2) affect discrimination between different groups (cognitively normal [CN], amnestic mild impairment [aMCI], AD)? (3) much variability explained diagnosis versus genotype? (4) Does relationship continuous measures performance differ