title: Alzheimer's disease--a panorama glimpse.
abstract: The single-mutation of genes associated with Alzheimer's disease (AD) increases the production of Aβ peptides. An elevated concentration of Aβ peptides is prone to aggregation into oligomers and further deposition as plaque. Aβ plaques and neurofibrillary tangles are two hallmarks of AD. In this review, we provide a broad overview of the diverses sources that could lead to AD, which include genetic origins, Aβ peptides and tau protein. We shall discuss on tau protein and tau accumulation, which result in neurofibrillary tangles. We detail the mechanisms of Aβ aggregation, fibril formation and its polymorphism. We then show the possible links between Aβ and tau pathology. Furthermore, we summarize the structural data of Aβ and its precursor protein obtained via Nuclear Magnetic Resonance (NMR) or X-ray crystallography. At the end, we go through the C-terminal and N-terminal truncated Aβ variants. We wish to draw reader's attention to two predominant and toxic Aβ species, namely Aβ4-42 and pyroglutamate amyloid-beta peptides, which have been neglected for more than a decade and may be crucial in Aβ pathogenesis due to their dominant presence in the AD brain.
authors.affiliation: School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637731, Singapore. zhao0139@e.ntu.edu.sg.
authors.forename: Li Na
authors.initials: LN
authors.lastname: Zhao
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551, Singapore. lylu@ntu.edu.sg.
authors.forename: Lanyuan
authors.initials: L
authors.lastname: Lu
authors.affiliation: School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637731, Singapore. lockyue@ntu.edu.sg.
authors.forename: Lock Yue
authors.initials: LY
authors.lastname: Chew
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551, Singapore. ygmu@ntu.edu.sg.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Mu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D006801:Humans; D018697:Nootropic Agents / Q000627:therapeutic use; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000737:chemistry; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D018697:Nootropic Agents; D020033:Protein Isoforms; D016875:tau Proteins; D011761:Pyrrolidonecarboxylic Acid