Impact of apolipoprotein E isoforms on sporadic Alzheimer's disease:beyond the role of amyloid beta  

作　　者：Madia Lozupone Francesco Panza 

机构地区：[1]Neurodegenerative Disease Unit,Department of Basic Medicine,Neuroscience,and Sense Organs,University of Bari Aldo Moro,Bari,Italy [2]Unit of Research Methodology and Data Sciences for Population Health,National Institute of Gastroenterology“Saverio de Bellis”,Research Hospital,Castellana Grotte,Bari,Italy

出　　处：《Neural Regeneration Research》2024年第1期80-83,共4页中国神经再生研究（英文版）

摘　　要：The impact of apolipoprotein E(ApoE)isoforms on sporadic Alzheimer's disease has long been studied;however,the influences of apolipoprotein E gene(APOE)on healthy and pathological human brains are not fully understood.ApoE exists as three common isoforms(ApoE2,ApoE3,and ApoE4),which differ in two amino acid residues.Traditionally,ApoE binds cholesterol and phospholipids and ApoE isoforms display diffe rent affinities for their receptors,lipids transport and distribution in the brain and periphery.The role of ApoE in the human depends on ApoE isoforms,brain regions,aging,and neural injury.APOE E4 is the strongest genetic risk factor for sporadic Alzheimer's disease,considering its role in influencing amyloid-beta metabolism.The exact mechanisms by which APOE gene variants may increase or decrease Alzheimer's disease risk are not fully understood,but APOE was also known to affect directly and indirectly tau-mediated neurodegeneration,lipids metabolism,neurovascular unit,and microglial function.Consistent with the biological function of ApoE,ApoE4 isoform significantly alte red signaling pathways associated with cholesterol homeostasis,transport,and myelination.Also,the rare protective APOE variants confirm that ApoE plays an important role in Alzheimer's disease pathogenesis.The objectives of the present mini-review were to describe classical and new roles of various ApoE isoforms in Alzheimer's disease pathophysiology beyond the deposition of amyloid-beta and to establish a functional link between APOE,brain function,and memory,from a molecular to a clinical level.APOE genotype also exerted a heterogeneous effect on clinical Alzheimer's disease phenotype and its outcomes.Not only in learning and memory but also in neuro psychiatric symptoms that occur in a premorbid condition.Cla rifying the relationships between Alzheimer's disease-related pathology with neuropsychiatric symptoms,particularly suicidal ideation in Alzheimer's disease patients,may be useful for elucidating also the underlying pathophysiological pro

关 键 词：Alzheimer's disease AMYLOID-BETA apolipoprotein E DEMENTIA glymphatic transport LIPIDS neuropsychiatric symptoms neurovascular unit tau protein 

分 类 号：R749.16[医药卫生—神经病学与精神病学]