RESUMO
INTRODUCTION: We aimed to investigate the effect of apolipoprotein E4 (APOE) ε4 on synaptic density in cognitively impaired (CI) participants. METHODS: One hundred ten CI participants underwent amyloid positron emission tomography (PET) with 18F-florbetapir and synaptic density PET with 18F-SynVesT-1. We evaluated the influence of APOE ε4 allele on synaptic density and investigated the effects of ε4 genotype on the associations of synaptic density with Alzheimer's disease (AD) biomarkers. The mediation effects of AD biomarkers on ε4-associated synaptic density loss were analyzed. RESULTS: Compared with non-carriers, APOE ε4 allele carriers exhibited significant synaptic loss in the medial temporal lobe. Amyloid beta (Aß) and tau pathology mediated the effects of APOE ε4 on synaptic density to different extents. The associations between synaptic density and tau pathology were regulated by the APOE ε4 genotype. DISCUSSION: The APOE ε4 allele was associated with decreased synaptic density in CI individuals and may be driven by AD biomarkers.
Assuntos
Peptídeos beta-Amiloides , Apolipoproteína E4 , Disfunção Cognitiva , Tomografia por Emissão de Pósitrons , Sinapses , Humanos , Masculino , Feminino , Apolipoproteína E4/genética , Idoso , Disfunção Cognitiva/genética , Disfunção Cognitiva/patologia , Sinapses/patologia , Sinapses/metabolismo , Peptídeos beta-Amiloides/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo , Genótipo , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Doença de Alzheimer/diagnóstico por imagem , Biomarcadores , Pessoa de Meia-Idade , Alelos , Idoso de 80 Anos ou mais , Encéfalo/patologia , Encéfalo/diagnóstico por imagemRESUMO
Alzheimer's Disease (AD), the leading cause of senile dementia, is a progressive neurodegenerative disorder affecting millions of people worldwide and exerting tremendous socioeconomic burden on all societies. Although definitive diagnosis of AD is often made in the presence of clinical manifestations in late stages, it is now universally believed that AD is a continuum of disease commencing from the preclinical stage with typical neuropathological alterations appearing decades prior to its first symptom, to the prodromal stage with slight symptoms of amnesia (amnestic mild cognitive impairment, aMCI), and then to the terminal stage with extensive loss of basic cognitive functions, i.e., AD-dementia. Positron emission tomography (PET) radiotracers have been developed in a search to meet the increasing clinical need of early detection and treatment monitoring for AD, with reference to the pathophysiological targets in Alzheimer's brain. These include the pathological aggregations of misfolded proteins such as ß-amyloid (Aß) plagues and neurofibrillary tangles (NFTs), impaired neurotransmitter system, neuroinflammation, as well as deficient synaptic vesicles and glucose utilization. In this article we survey the various PET radiotracers available for AD imaging and discuss their clinical applications especially in terms of early detection and cognitive relevance.
RESUMO
This article describes the application of various PET imaging agents in the investigation and diagnosis of Alzheimer's disease (AD), including radiotracers for pathologic biomarkers of AD such as ß-amyloid deposits and tau protein aggregates, and the neuroinflammation biomarker 18 kDa translocator protein, as well as physiologic biomarkers, such as cholinergic receptors, glucose metabolism, and the synaptic density biomarker synaptic vesicle glycoprotein 2A. Potential of these biomarkers for early AD diagnosis is also assessed.
