Displaying publications 41 - 60 of 514 in total

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  1. Chai TT, Xiao J, Mohana Dass S, Teoh JY, Ee KY, Ng WJ, et al.
    Food Chem, 2021 Mar 15;340:127876.
    PMID: 32871354 DOI: 10.1016/j.foodchem.2020.127876
    Jackfruit is a sweet tropical fruit with very pleasant aroma, and the ripe seeds are edible. In this study, jackfruit seed proteins were isolated and subjected to trypsin digestion. The resultant protein hydrolysate was then subjected to antioxidant assay-guided purification, using centrifugal filtration, C18 reverse-phase and strong cation exchange (SCX) fractionations. The purified SCX fraction was further analyzed by de novo peptide sequencing, and two peptide sequences were identified and synthesized. Peptide JFS-2 (VGPWQK) was detected with antioxidant potential, with EC50 value comparable to that of commercial GSH antioxidant peptide. Additionally, the identified peptides were tested with protein protection potential, in an albumin protein denaturation inhibitory assay. Concurrently, we also investigated the pH, temperature, and gastrointestinal-digestion stability profiles for the identified peptide. With further research efforts, the identified peptides could potentially be developed into preservative agent for protein-rich food systems or as health-promoting diet supplements.
    Matched MeSH terms: Peptides/analysis*; Peptides/metabolism; Peptides/chemistry*
  2. Che Aziz Ali, Kamal Roslan Mohamed, Nurul Afifah Mohd Radzir
    Sains Malaysiana, 2018;47:1387-1392.
    Analisis geokimia menggunakan kaedah ICP-MS menunjukkan taburan geokimia unsur di kawasan kajian dipengaruhi
    oleh dua asalan sedimen berbeza iaitu daripada marin dan daratan. Unsur Ca dan Mg dikenal pasti sebagai unsur
    marin, manakala unsur Al, Fe, Mn, Na, Cu, Cr, Zn dan Ni dikenal pasti sebagai unsur daratan. Unsur Ca dan Mg dikenal
    pasti terhasil daripada proses penyahkapuran rangka dan hidupan marin seperti cengkerang moluska dan foraminifera.
    Unsur benua berasal daripada granit dari Gunung Korbu dan Gunung Stong yang disaliri oleh Sungai Nenggiri dan
    Sungai Galas, serta batuan argilit arenit yang berasal dari bahagian selatan dan tenggara Negeri Kelantan dari
    Gunung Cintawangsa dan Gunung Stong dan disaliri oleh Sungai Lebir dan Sungai Galas. Unsur daripada batuan
    induk membebaskan unsur kimia semasa luluhawa kimia dan telah dijerap oleh cas-cas negatif pada permukaan sedimen
    halus seperti lempung dan lodak sebelum dimendapkan bersama di dalam kawasan kajian.
    Matched MeSH terms: Peptides
  3. Ahmad Nadzirin I, Chor ALT, Salleh AB, Rahman MBA, Tejo BA
    Comput Biol Chem, 2021 Jun;92:107487.
    PMID: 33957477 DOI: 10.1016/j.compbiolchem.2021.107487
    Rheumatoid arthritis (RA) is an inflammatory autoimmune disease affecting about 0.24 % of the world population. Protein arginine deiminase type 4 (PAD4) is believed to be responsible for the occurrence of RA by catalyzing citrullination of proteins. The citrullinated proteins act as autoantigens by stimulating an immune response. Citrullinated α-enolase has been identified as one of the autoantigens for RA. Hence, α-enolase serves as a suitable template for design of potential peptide inhibitors against PAD4. The binding affinity of α-enolase-derived peptides and PAD4 was virtually determined using PatchDock and HADDOCK docking programs. Synthesis of the designed peptides was performed using a solid phase peptide synthesis method. The inhibitory potential of each peptide was determined experimentally by PAD4 inhibition assay and IC50 measurement. PAD4 assay data show that the N-P2 peptide is the most favourable substrate among all peptides. Further modification of N-P2 by changing the Arg residue to canavanine [P2 (Cav)] rendered it an inhibitor against PAD4 by reducing the PAD4 activity to 35 % with IC50 1.39 mM. We conclude that P2 (Cav) is a potential inhibitor against PAD4 and can serve as a starting point for the development of even more potent inhibitors.
    Matched MeSH terms: Peptides/metabolism; Peptides/pharmacology*; Peptides/chemistry
  4. Andruszkiewicz PJ, D'Souza RN, Corno M, Kuhnert N
    Food Res Int, 2020 07;133:109164.
    PMID: 32466895 DOI: 10.1016/j.foodres.2020.109164
    Chemical transformations of Amadori compounds are responsible for the formation of aroma volatiles at the end of the Maillard reaction cascade, which in turn contributes to unique organoleptic characteristics of chocolate. A large amount of short peptides reported in fermented cocoa suggests the existence of a much larger variety of these flavor precursors than previously suspected. An HPLC-MS-MS study was performed on dried Malaysian cocoa beans to identify novel Amadori and Heyns compounds. In total, 34 species were found, including 26 previously unknown derived from di- and tripeptides. We illustrate how the structures were elucidated via tandem MS experiments, as well as present a comparative study on their relative quantities in samples coming from 11 countries of origin. There were significant differences between them, and discrimination was possible by principal component analysis based on Amadori content alone. However, the PCA separation could be a result of various post-harvest practices exerted among said countries.
    Matched MeSH terms: Peptides
  5. Zaman R, Islam RA, Ibnat N, Othman I, Zaini A, Lee CY, et al.
    J Control Release, 2019 05 10;301:176-189.
    PMID: 30849445 DOI: 10.1016/j.jconrel.2019.02.016
    Macromolecular protein and peptide therapeutics have been proven to be effective in treating critical human diseases precisely. Thanks to biotechnological advancement, a huge number of proteins and peptide therapeutics were made their way to pharmaceutical market in past few decades. However, one of the biggest challenges to be addressed for protein therapeutics during clinical application is their fast degradation in serum and quick elimination owing to enzymatic degradation, renal clearance, liver metabolism and immunogenicity, attributing to the short half-lives. Size and hydrophobicity of protein molecules make them prone to kidney filtration and liver metabolism. On the other hand, proteasomes responsible for protein destruction possess the capability of specifically recognizing almost all kinds of foreign proteins while avoiding any unwanted destruction of cellular components. At present almost all protein-based drug formulations available in market are administered intravenously (IV) or subcutaneously (SC) with high dosing at frequent interval, eventually creating dose-fluctuation-related complications and reducing patient compliance vastly. Therefore, artificially increasing the therapeutic half-life of a protein by attaching to it a molecule that increases the overall size (eg, PEG) or helps with receptor mediated recycling (eg, albumin), or manipulating amino acid chain in a way that makes it more prone towards aggregate formation, are some of the revolutionary approaches to avoid the fast degradation in vivo. Half-life extension technologies that are capable of dramatically enhancing half-lives of proteins in circulation (2-100 folds) and thus improving their overall pharmacokinetic (PK) parameters have been successfully applied on a wide range of protein therapeutics from hormones and enzymes, growth factor, clotting factor to interferon. The focus of the review is to assess the technological advancements made so far in enhancing circulatory half-lives and improving therapeutic potency of proteins.
    Matched MeSH terms: Peptides/pharmacokinetics*; Peptides/therapeutic use; Peptides/chemistry
  6. Md S, Mustafa G, Baboota S, Ali J
    Drug Dev Ind Pharm, 2015;41(12):1922-34.
    PMID: 26057769 DOI: 10.3109/03639045.2015.1052081
    Brain disorders remain the world's leading cause of disability, and account for more hospitalizations and prolonged care than almost all other diseases combined. The majority of drugs, proteins and peptides do not readily permeate into brain due to the presence of the blood-brain barrier (BBB), thus impeding treatment of these conditions.
    Matched MeSH terms: Peptides
  7. Velayutham M, Priya PS, Sarkar P, Murugan R, Almutairi BO, Arokiyaraj S, et al.
    Molecules, 2023 Sep 21;28(18).
    PMID: 37764521 DOI: 10.3390/molecules28186746
    Small molecules as well as peptide-based therapeutic approaches have attracted global interest due to their lower or no toxicity in nature, and their potential in addressing several health complications including immune diseases, cardiovascular diseases, metabolic disorders, osteoporosis and cancer. This study proposed a peptide, GE18 of subtilisin-like peptidase from the virulence factor of aquatic pathogenic fungus Aphanomyces invadans, which elicits anti-cancer and anti-microbial activities. To understand the potential GE18 peptide-induced biological effects, an in silico analysis, in vitro (L6 cells) and in vivo toxicity assays (using zebrafish embryo), in vitro anti-cancer assays and anti-microbial assays were performed. The outcomes of the in silico analyses demonstrated that the GE18 peptide has potent anti-cancer and anti-microbial activities. GE18 is non-toxic to in vitro non-cancerous cells and in vivo zebrafish larvae. However, the peptide showed significant anti-cancer properties against MCF-7 cells with an IC50 value of 35.34 µM, at 24 h. Besides the anti-proliferative effect on cancer cells, the peptide exposure does promote the ROS concentration, mitochondrial membrane potential and the subsequent upregulation of anti-cancer genes. On the other hand, GE18 elicits significant anti-microbial activity against P. aeruginosa, wherein GE18 significantly inhibits bacterial biofilm formation. Since the peptide has positively charged amino acid residues, it targets the cell membrane, as is evident in the FESEM analysis. Based on these outcomes, it is possible that the GE18 peptide is a significant anti-cancer and anti-microbial molecule.
    Matched MeSH terms: Peptides
  8. Hosseinzadeh A, Zamani A, Johari HG, Vaez A, Golchin A, Tayebi L, et al.
    Cell Biochem Funct, 2023 Jul;41(5):517-541.
    PMID: 37282756 DOI: 10.1002/cbf.3816
    Hyperglycemia, a distinguishing feature of diabetes mellitus that might cause a diabetic foot ulcer (DFU), is an endocrine disorder that affects an extremely high percentage of people. Having a comprehensive understanding of the molecular mechanisms underlying the pathophysiology of diabetic wound healing can help researchers and developers design effective therapeutic strategies to treat the wound healing process in diabetes patients. Using nanoscaffolds and nanotherapeutics with dimensions ranging from 1 to 100 nm represents a state-of-the-art and viable therapeutic strategy for accelerating the wound healing process in diabetic patients, particularly those with DFU. Nanoparticles can interact with biological constituents and infiltrate wound sites owing to their reduced diameter and enhanced surface area. Furthermore, it is noteworthy that they promote the processes of vascularization, cellular proliferation, cell signaling, cell-to-cell interactions, and the formation of biomolecules that are essential for effective wound healing. Nanomaterials possess the ability to effectively transport and deliver various pharmacological agents, such as nucleic acids, growth factors, antioxidants, and antibiotics, to specific tissues, where they can be continuously released and affect the wound healing process in DFU. The present article elucidates the ongoing endeavors in the field of nanoparticle-mediated therapies for the management of DFU.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins
  9. Tan FHP, Najimudin N, Watanabe N, Shamsuddin S, Azzam G
    Behav Brain Res, 2023 Aug 24;452:114568.
    PMID: 37414223 DOI: 10.1016/j.bbr.2023.114568
    Alzheimer's disease (AD) is the most common neurodegenerative condition in civilizations worldwide. The distinctive occurrence of amyloid-beta (Aβ) accumulation into insoluble fibrils is part of the disease pathophysiology with Aβ42 being the most toxic and aggressive Aβ species. The polyphenol, p-Coumaric acid (pCA), has been known to boost a number of therapeutic benefits. Here, pCA's potential to counteract the negative effects of Aβ42 was investigated. First, pCA was confirmed to reduce Aβ42 fibrillation using an in vitro activity assay. The compound was next examined on Aβ42-exposed PC12 neuronal cells and was found to significantly decrease Aβ42-induced cell mortality. pCA was then examined using an AD Drosophila melanogaster model. Feeding of pCA partially reversed the rough eye phenotype, significantly lengthened AD Drosophila's lifespan, and significantly enhanced the majority of the AD Drosophila's mobility in a sex-dependent manner. The findings of this study suggest that pCA may have therapeutic benefits for AD.
    Matched MeSH terms: Amyloid beta-Peptides
  10. Ariffin N, Newman DW, Nelson MG, O'cualain R, Hubbard SJ
    J Proteome Res, 2024 May 03;23(5):1583-1592.
    PMID: 38651221 DOI: 10.1021/acs.jproteome.3c00675
    MD2 pineapple (Ananas comosus) is the second most important tropical crop that preserves crassulacean acid metabolism (CAM), which has high water-use efficiency and is fast becoming the most consumed fresh fruit worldwide. Despite the significance of environmental efficiency and popularity, until very recently, its genome sequence has not been determined and a high-quality annotated proteome has not been available. Here, we have undertaken a pilot proteogenomic study, analyzing the proteome of MD2 pineapple leaves using liquid chromatography-mass spectrometry (LC-MS/MS), which validates 1781 predicted proteins in the annotated F153 (V3) genome. In addition, a further 603 peptide identifications are found that map exclusively to an independent MD2 transcriptome-derived database but are not found in the standard F153 (V3) annotated proteome. Peptide identifications derived from these MD2 transcripts are also cross-referenced to a more recent and complete MD2 genome annotation, resulting in 402 nonoverlapping peptides, which in turn support 30 high-quality gene candidates novel to both pineapple genomes. Many of the validated F153 (V3) genes are also supported by an independent proteomics data set collected for an ornamental pineapple variety. The contigs and peptides have been mapped to the current F153 genome build and are available as bed files to display a custom gene track on the Ensembl Plants region viewer. These analyses add to the knowledge of experimentally validated pineapple genes and demonstrate the utility of transcript-derived proteomics to discover both novel genes and genetic structure in a plant genome, adding value to its annotation.
    Matched MeSH terms: Peptides/analysis; Peptides/genetics; Peptides/chemistry
  11. Jindal HM, Le CF, Mohd Yusof MY, Velayuthan RD, Lee VS, Zain SM, et al.
    PLoS One, 2015;10(6):e0128532.
    PMID: 26046345 DOI: 10.1371/journal.pone.0128532
    Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics in order to defeat multidrug-resistant bacteria such as Streptococcus pneumoniae. In this study, thirteen antimicrobial peptides were designed based on two natural peptides indolicidin and ranalexin. Our results revealed that four hybrid peptides RN7-IN10, RN7-IN9, RN7-IN8, and RN7-IN6 possess potent antibacterial activity against 30 pneumococcal clinical isolates (MIC 7.81-15.62µg/ml). These four hybrid peptides also showed broad spectrum antibacterial activity (7.81µg/ml) against S. aureus, methicillin resistant S. aureus (MRSA), and E. coli. Furthermore, the time killing assay results showed that the hybrid peptides were able to eliminate S. pneumoniae within less than one hour which is faster than the standard drugs erythromycin and ceftriaxone. The cytotoxic effects of peptides were tested against human erythrocytes, WRL-68 normal liver cell line, and NL-20 normal lung cell line. The results revealed that none of the thirteen peptides have cytotoxic or hemolytic effects at their MIC values. The in silico molecular docking study was carried out to investigate the binding properties of peptides with three pneumococcal virulent targets by Autodock Vina. RN7IN6 showed a strong affinity to target proteins; autolysin, pneumolysin, and pneumococcal surface protein A (PspA) based on rigid docking studies. Our results suggest that the hybrid peptides could be suitable candidates for antibacterial drug development.
    Matched MeSH terms: Peptides/pharmacology; Peptides/chemistry*; Peptides, Cyclic/chemistry*; Antimicrobial Cationic Peptides/chemistry*
  12. Shintani M, Minaguchi K, Suzuki K, Lim KA
    Biochem Genet, 1990 Apr;28(3-4):173-84.
    PMID: 2383244
    Three new variants of acidic proline-rich proteins (At, Au, Aw) were found in human parotid saliva by isoelectric focusing and basic gel electrophoresis. Electrophoretic comparison of the purified proteins and their tryptic peptides suggested minor charge and size differences from other acidic PRPs. Genetic and biochemical studies indicate that the At and Aw proteins are allelic products of the PRH1 locus. Gene frequencies of the At productive allele (PRH1(6)) in Japanese, Chinese, and Malays were 0.008, 0.012, and 0.004, respectively. The Au protein was also found in Japanese (2 in 746 samples), Chinese (1 in 215 samples), and Malays (1 in 220 samples), however, the Aw protein was found only in one Japanese (n = 746). These three proteins were not found in 106 Indian subjects.
    Matched MeSH terms: Peptides/genetics*; Peptides/isolation & purification; Salivary Proteins and Peptides/genetics*
  13. Sadek MM, Barlow N, Leung EWW, Williams-Noonan BJ, Yap BK, Shariff FM, et al.
    ACS Chem. Biol., 2018 10 19;13(10):2930-2938.
    PMID: 30226743 DOI: 10.1021/acschembio.8b00561
    SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, and SPSB4 interact with inducible nitric oxide synthase (iNOS), causing the iNOS to be polyubiquitinated and targeted for degradation. Inhibition of this interaction increases iNOS levels, and consequently cellular nitric oxide (NO) concentrations, and has been proposed as a potential strategy for killing intracellular pathogens. We previously described two DINNN-containing cyclic peptides (CP1 and CP2) as potent inhibitors of the murine SPSB-iNOS interaction. In this study, we report the crystal structures of human SPSB4 bound to CP1 and CP2 and human SPSB2 bound to CP2. We then used these structures to design a new inhibitor in which an intramolecular hydrogen bond was replaced with a hydrocarbon linkage to form a smaller macrocycle while maintaining the bound geometry of CP2 observed in the crystal structures. This resulting pentapeptide SPSB-iNOS inhibitor (CP3) has a reduced macrocycle ring size, fewer nonbinding residues, and includes additional conformational constraints. CP3 has a greater affinity for SBSB2 ( KD = 7 nM as determined by surface plasmon resonance) and strongly inhibits the SPSB2-iNOS interaction in macrophage cell lysates. We have also determined the crystal structure of CP3 in complex with human SPSB2, which reveals the structural basis for the increased potency of CP3 and validates the original design.
    Matched MeSH terms: Peptides, Cyclic/pharmacology; Peptides, Cyclic/chemistry*; Intracellular Signaling Peptides and Proteins/metabolism; Intracellular Signaling Peptides and Proteins/chemistry*
  14. Anada RP, Wong KT, Malicdan MC, Goh KJ, Hayashi Y, Nishino I, et al.
    Amyloid, 2014 Jun;21(2):138-9.
    PMID: 24601867 DOI: 10.3109/13506129.2014.889675
    Matched MeSH terms: Amyloid beta-Peptides/metabolism*
  15. Nur Azira T, Che Man YB, Raja Mohd Hafidz RN, Aina MA, Amin I
    Food Chem, 2014 May 15;151:286-92.
    PMID: 24423534 DOI: 10.1016/j.foodchem.2013.11.066
    The study was aimed to differentiate between porcine and bovine gelatines in adulterated samples by utilising sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) combined with principal component analysis (PCA). The distinct polypeptide patterns of 6 porcine type A and 6 bovine type B gelatines at molecular weight ranged from 50 to 220 kDa were studied. Experimental samples of raw gelatine were prepared by adding porcine gelatine in a proportion ranging from 5% to 50% (v/v) to bovine gelatine and vice versa. The method used was able to detect 5% porcine gelatine added to the bovine gelatine. There were no differences in the electrophoretic profiles of the jelly samples when the proteins were extracted with an acetone precipitation method. The simple approach employing SDS-PAGE and PCA reported in this paper may provide a useful tool for food authenticity issues concerning gelatine.
    Matched MeSH terms: Peptides/chemistry*
  16. Yoshikawa K, Tao S, Arihara S
    J Nat Prod, 2000 Apr;63(4):540-2.
    PMID: 10785436
    The stem of Stephanotis floribunda afforded a new cyclic pentapeptide stephanotic acid (1), possessing a novel 6-(leucin-3'-yl) tryptophan skeleton. The structure of 1 was assigned on the basis of extensive NMR experiments and a chemical reaction and shown to be closely related to the bicyclic octapeptide moroidin (3), a toxin from Laportea moroides.
    Matched MeSH terms: Peptides, Cyclic/chemistry*
  17. Dahiya R, Dahiya S, Fuloria NK, Kumar S, Mourya R, Chennupati SV, et al.
    Mar Drugs, 2020 Jun 24;18(6).
    PMID: 32599909 DOI: 10.3390/md18060329
    Peptides are distinctive biomacromolecules that demonstrate potential cytotoxicity and diversified bioactivities against a variety of microorganisms including bacteria, mycobacteria, and fungi via their unique mechanisms of action. Among broad-ranging pharmacologically active peptides, natural marine-originated thiazole-based oligopeptides possess peculiar structural features along with a wide spectrum of exceptional and potent bioproperties. Because of their complex nature and size divergence, thiazole-based peptides (TBPs) bestow a pivotal chemical platform in drug discovery processes to generate competent scaffolds for regulating allosteric binding sites and peptide-peptide interactions. The present study dissertates on the natural reservoirs and exclusive structural components of marine-originated TBPs, with a special focus on their most pertinent pharmacological profiles, which may impart vital resources for the development of novel peptide-based therapeutic agents.
    Matched MeSH terms: Peptides/chemistry*
  18. Ishima Y, Mimono A, Tuan Giam Chuang V, Fukuda T, Kusumoto K, Okuhira K, et al.
    IUBMB Life, 2020 04;72(4):641-651.
    PMID: 31794135 DOI: 10.1002/iub.2203
    Deposition of amyloid protein, particularly Aβ1-42 , is a major contributor to the onset of Alzheimer's disease (AD). However, almost no deposition of Aβ in the peripheral tissues could be found. Human serum albumin (HSA), the most abundant protein in the blood, has been reported to inhibit amyloid formation through binding Aβ, which is believed to play an important role in the peripheral clearance of Aβ. We identified the Aβ binding site on HSA and developed HSA mutants with high binding capacities for Aβ using a phage display method. HSA fragment 187-385 (Domain II) was found to exhibit the highest binding capacity for Aβ compared with the other two HSA fragments. To elucidate the sequence that forms the binding site for Aβ on Domain II, a random screening of Domain II display phage biopanning was constructed. A number of mutants with higher Aβ binding capacities than the wild type were identified. These mutants exhibited stronger scavenging abilities than the wild type, as revealed via in vitro equilibrium dialysis of Aβ experiments. These findings provide useful basic data for developing a safer alternative therapy than Aβ vaccines and for application in plasma exchange as well as extracorporeal dialysis.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism*
  19. Mohd Lazaldin MA, Iezhitsa I, Agarwal R, Bakar NS, Agarwal P, Mohd Ismail N
    Eur J Neurosci, 2020 06;51(12):2394-2411.
    PMID: 31883161 DOI: 10.1111/ejn.14662
    Brain-derived neurotrophic factor (BDNF) could be considered a potential neuroprotective therapy in amyloid beta (Aβ)-associated retinal and optic nerve degeneration. Hence, in this study we investigated the neuroprotective effect of BDNF against Aβ1-40-induced retinal and optic nerve injury. In this study, exposure to Aβ1-40 was associated with retinal and optic nerve injury. TUNEL staining showed significant reduction in the apoptotic cell count in the BDNF-treated group compared with Aβ1-40 group. H&E-stained retinal sections also showed a striking reduction in neuronal cells in the ganglion cell layer (GCL) of retinas fourteen days after Aβ1-40 exposure. By contrast, number of retinal cells was preserved in the retinas of BDNF-treated animals. After Aβ1-40 exposure, visible axonal swelling was observed in optic nerve sections. However, the BDNF-treated group showed fewer changes in optic nerve; axonal swelling was less frequent and less marked. In the present study, exposure to Aβ was associated with oxidative stress, whereas levels of retinal glutathione (GSH), superoxide dismutase (SOD) and catalase were significantly increased in BDNF-treated than in Aβ1-40-treated rats. Both visual object recognition tests using an open-field arena and a Morris water maze showed that BDNF improved rats' ability to recognise visual cues (objects with different shapes) after Aβ1-40 exposure, thus demonstrating that the visual performance of rats was relatively preserved following BDNF treatment. In conclusion, intravitreal treatment with BDNF prevents Aβ1-40-induced retinal cell apoptosis and axon loss in the optic nerve of rats by reducing retinal oxidative stress and restoring retinal BDNF levels.
    Matched MeSH terms: Amyloid beta-Peptides/toxicity
  20. Kim SE, Lee B, Jang H, Chin J, Khoo CS, Choe YS, et al.
    Alzheimers Res Ther, 2021 02 19;13(1):48.
    PMID: 33608041 DOI: 10.1186/s13195-021-00787-7
    BACKGROUND: The presence of ß-amyloid (Aß) in the brain can be identified using amyloid PET. In clinical practice, the amyloid PET is interpreted based on dichotomous visual rating, which renders focal Aß accumulation be read as positive for Aß. However, the prognosis of patients with focal Aß deposition is not well established. Thus, we investigated cognitive trajectories of patients with focal Aß deposition.

    METHODS: We followed up 240 participants (112 cognitively unimpaired [CU], 78 amnestic mild cognitive impairment [aMCI], and 50 Alzheimer's disease (AD) dementia [ADD]) for 2 years from 9 referral centers in South Korea. Participants were assessed with neuropsychological tests and 18F-flutemetamol (FMM) positron emission tomography (PET). Ten regions (frontal, precuneus/posterior cingulate (PPC), lateral temporal, parietal, and striatum of each hemisphere) were visually examined in the FMM scan, and participants were divided into three groups: No-FMM, Focal-FMM (FMM uptake in 1-9 regions), and Diffuse-FMM. We used mixed-effects model to investigate the speed of cognitive decline in the Focal-FMM group according to the cognitive level, extent, and location of Aß involvement, in comparison with the No- or Diffuse-FMM group.

    RESULTS: Forty-five of 240 (18.8%) individuals were categorized as Focal-FMM. The rate of cognitive decline in the Focal-FMM group was faster than the No-FMM group (especially in the CU and aMCI stage) and slower than the Diffuse-FMM group (in particular in the CU stage). Within the Focal-FMM group, participants with FMM uptake to a larger extent (7-9 regions) showed faster cognitive decline compared to those with uptake to a smaller extent (1-3 or 4-6 regions). The Focal-FMM group was found to have faster cognitive decline in comparison with the No-FMM when there was uptake in the PPC, striatum, and frontal cortex.

    CONCLUSIONS: When predicting cognitive decline of patients with focal Aß deposition, the patients' cognitive level, extent, and location of the focal involvement are important.

    Matched MeSH terms: Amyloid beta-Peptides/metabolism
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