Aβ42 and Aβ40: similarities and differences

Abstract

The abnormal accumulation of amyloid-β (Aβ) peptide in the brain is one of the most important hallmarks of Alzheimer's disease. Aβ is an aggregation-prone and toxic polypeptide with 39-43 residues, derived from the amyloid precursor protein proteolysis process. According to the amyloid hypothesis, abnormal accumulation of Aβ in the brain is the primary influence driving Alzheimer's disease pathologies. Among all kinds of Aβ isoforms, Aβ40 and Aβ42 are believed to be the most important ones. Although these two kinds of Aβ differ only in two amino acid residues, recent studies show that they differ significantly in their metabolism, physiological functions, toxicities, and aggregation mechanism. In this review, we mainly summarize the similarities and differences between Aβ42 and Aβ40, recent studies on selective inhibitors as well as probes will also be mentioned.

Rhynchophylline Protects Against the Amyloid β-Induced Increase of Spontaneous Discharges in the Hippocampal CA1 Region of Rats

“…Ab 1-42 is one of the most toxic Ab fragments detectable in the brains of AD patients [23]. Additionally, it possesses many characteristics of full length Ab, including aggregation ability, capability to cause memory impairment, neural hyperexcitability, cholinergic dysfunction, oxidative stress, and morphological alterations, among others [2,24,25]. For these reasons, soluble Ab 1-42 was used to create AD animal model in this present study.…”

The Role of Microglia in Retinal Neurodegeneration: Alzheimer's Disease, Parkinson, and Glaucoma

“…In AD patients, the alloform Aβ42 is increased (Alexandrov et al, 2011). This alloform presents higher cellular toxicity, more aggregation capacity, and a more direct relation with AD pathology (Qiu et al, 2015). Aβ42 peptide accumulation in the retina may contribute to retinal degeneration and visual impairment in AD (Hardy and Selkoe, 2002; Selkoe, 2004, 2008; Alexandrov et al, 2011; Ratnayaka et al, 2015; Hart et al, 2016; Figure 1A, Table 1).…”

Molecular insights into the effect L17A/F19A double mutation on the structure and dynamics of Aβ40: A molecular dynamics simulation study

“…44 The ensembleaveraged 3 J NH-Hα coupling constants of the Aβ 40 residues were calculated ( Figure 2C) and compared with NMR data. 44 The theoretical 3 The RDC constants computed from Aβ 40 simulations are compared with Aβ 40 experimental RDC constants. 44 The RDC measurements investigate the orientation of amide NH bonds in protein backbones with respect to the external magnetic field and can identify long-range structural correlations across the biomolecular structure.…”

“…The Aβ peptides are a proteolytic byproduct of the transmembrane amyloid precursor protein and mainly composed of Aβ 40 and Aβ 42 comprising 40 and 42 residues, respectively. The most abundant form is Aβ 40 that comprise about 90% of all Aβ species in cerebrospinal fluid . All Aβ peptides are highly amyloidogenic and play a critical role in amyloid cascade hypothesis that highlight AD pathogenesis as a multistage aggregation of Aβ species.…”

“…The most abundant form is Aβ 40 that comprise about 90% of all Aβ species in cerebrospinal fluid. 3 All Aβ peptides are highly amyloidogenic 4 and play a critical role in amyloid cascade hypothesis that highlight AD pathogenesis as a multistage aggregation of Aβ species. The Aβ monomers exist as a random coil in physiological buffers, however, aggregate to form amyloid fibrils with a cross β-sheet structure which is the major cause of plaque formation and toxicity.…”