CoChat
Sign Up
Cited by 141Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Amyloid Precursor Protein and Alzheimer’s Disease

Open access
Orobets, Kseniia S., Karamyshev, Andrey L.·2023·International Journal of Molecular Sciences
DOI 10.3390/ijms241914794PMC PMC10573485
Open this paper in CoChat — free accountOpen PDF

Abstract

Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders associated with age or inherited mutations. It is characterized by severe dementia in the late stages that affect memory, cognitive functions, and daily life overall. AD progression is linked to the accumulation of cytotoxic amyloid beta (Aβ) and hyperphosphorylated tau protein combined with other pathological features such as synaptic loss, defective energy metabolism, imbalances in protein, and metal homeostasis. Several treatment options for AD are under investigation, including antibody-based therapy and stem cell transplantation. Amyloid precursor protein (APP) is a membrane protein considered to play a main role in AD pathology. It is known that APP in physiological conditions follows a non-amyloidogenic pathway; however, it can proceed to an amyloidogenic scenario, which leads to the generation of extracellular deleterious Aβ plaques. Not all steps of APP biogenesis are clear so far, and these questions should be addressed in future studies. AD is a complex chronic disease with many factors that contribute to disease progression.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3390/ijms241914794

Cites

16 of 16 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Mutations in APP and presenilin genes increase Aβ production or alter the Aβ42/Aβ40 ratio, causing early-onset familial AD.

    “Mutations in the APP and presenilin genes increase Aβ production or alter the Aβ42/Aβ40 ratio, causing early-onset familial AD [30].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [30]

    The Genetics of Alzheimer’s Disease (section 2; page unavailable) links APP and PSEN1/PSEN2 mutations to familial AD. It says APP mutations can increase Aβ42 production and presenilin mutations affect cleavage, favoring longer Aβ peptides; the Introduction identifies familial AD as early-onset. The copy does not explicitly state that these mutations alter the Aβ42/Aβ40 ratio. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 141

  1. [2]Rajan K.B. Weuve J. Barnes L.L. McAninch E.A. Wilson R.S. Evans D.A. Population estimate of people with clinical Alzheimer’s disease and mild cognitive impairment in the United States (2020–2060) Alzheimers Dement. 2021 17 1966 1975 10.1002/alz.12362 34043283 PMC9013315 · DOI · Paper page
  2. [5]Course M.M. Gudsnuk K. Keene C.D. Bird T.D. Jayadev S. Valdmanis P.N. Aberrant splicing of PSEN2, but not PSEN1, in individuals with sporadic Alzheimer’s disease Brain 2023 146 507 518 10.1093/brain/awac294 35949106 PMC10169283 · DOI
  3. [6]Jia J. Zhang Y. Shi Y. Yin X. Wang S. Li Y. Zhao T. Liu W. Zhou A. Jia L. A 19-Year-Old Adolescent with Probable Alzheimer’s Disease J. Alzheimers Dis. 2023 91 915 922 10.3233/JAD-221065 36565128 · DOI
  4. [7]Csaban D. Illes A. Renata T.B. Balicza P. Pentelenyi K. Molnar V. Gezsi A. Grosz Z. Gal A. Kovacs T. Genetic landscape of early-onset dementia in Hungary Neurol. Sci. 2022 43 5289 5300 10.1007/s10072-022-06168-8 35752680 PMC9385840 · DOI
  5. [8]Barthélemy N.R. Li Y. Joseph-Mathurin N. Gordon B.A. Hassenstab J. Benzinger T.L.S. Buckles V. Fagan A.M. Perrin R.J. Goate A.M. A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease Nat. Med. 2020 26 398 407 10.1038/s41591-020-0781-z 32161412 PMC7309367 · DOI · Paper page
  6. [9]Gordon B.A. Blazey T.M. Su Y. Hari-Raj A. Dincer A. Flores S. Christensen J. McDade E. Wang G. Xiong C. Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer’s disease: A longitudinal study Lancet Neurol. 2018 17 241 250 10.1016/S1474-4422(18)30028-0 29397305 PMC5816717 · DOI · Paper page
  7. [10]Porsteinsson A.P. Isaacson R.S. Knox S. Sabbagh M.N. Rubino I. Diagnosis of Early Alzheimer’s Disease: Clinical Practice in 2021 J. Prev. Alzheimers Dis. 2021 8 371 386 10.14283/jpad.2021.23 34101796 · DOI · Paper page
  8. [12]Hardy J.A. Higgins G.A. Alzheimer’s disease: The amyloid cascade hypothesis Science 1992 256 184 185 10.1126/science.1566067 1566067 · DOI · Paper page
  9. [13]Edwards F.A. A Unifying Hypothesis for Alzheimer’s Disease: From Plaques to Neurodegeneration Trends Neurosci. 2019 42 310 322 10.1016/j.tins.2019.03.003 31006494 · DOI · Paper page
  10. [14]Busche M.A. Hyman B.T. Synergy between amyloid-β and tau in Alzheimer’s disease Nat. Neurosci. 2020 23 1183 1193 10.1038/s41593-020-0687-6 32778792 PMC11831977 · DOI · Paper page
  11. [15]Bertram L. McQueen M.B. Mullin K. Blacker D. Tanzi R.E. Systematic meta-analyses of Alzheimer disease genetic association studies: The AlzGene database Nat. Genet. 2007 39 17 23 10.1038/ng1934 17192785 · DOI · Paper page
  12. [16]Hollingworth P. Harold D. Sims R. Gerrish A. Lambert J.C. Carrasquillo M.M. Abraham R. Hamshere M.L. Pahwa J.S. Moskvina V. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease Nat. Genet. 2011 43 429 435 10.1038/ng.803 21460840 PMC3084173 · DOI · Paper page
  13. [18]Selkoe D.J. SnapShot: Pathobiology of Alzheimer’s disease Cell 2013 154 468 468.e1 10.1016/j.cell.2013.07.003 23870132 · DOI · Paper page
  14. [19]Waring S.C. Rosenberg R.N. Genome-wide association studies in Alzheimer disease Arch. Neurol. 2008 65 329 334 10.1001/archneur.65.3.329 18332245 · DOI
  15. [22]Mishra S. Knupp A. Szabo M.P. Williams C.A. Kinoshita C. Hailey D.W. Wang Y. Andersen O.M. Young J.E. The Alzheimer’s gene SORL1 is a regulator of endosomal traffic and recycling in human neurons Cell. Mol. Life Sci. 2022 79 162 10.1007/s00018-022-04182-9 35226190 PMC8885486 · DOI
  16. [23]Dib S. Pahnke J. Gosselet F. Role of ABCA7 in Human Health and in Alzheimer’s Disease Int. J. Mol. Sci. 2021 22 4603 10.3390/ijms22094603 33925691 PMC8124837 · DOI
  17. [24]Zhao N. Liu C.C. Qiao W. Bu G. Apolipoprotein E, Receptors, and Modulation of Alzheimer’s Disease Biol. Psychiatry 2018 83 347 357 10.1016/j.biopsych.2017.03.003 28434655 PMC5599322 · DOI · Paper page
  18. [25]Cataldo A.M. Peterhoff C.M. Troncoso J.C. Gomez-Isla T. Hyman B.T. Nixon R.A. Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer’s disease and Down syndrome: Differential effects of APOE genotype and presenilin mutations Am. J. Pathol. 2000 157 277 286 10.1016/S0002-9440(10)64538-5 10880397 PMC1850219 · DOI
  19. [29]Zhao J. Fu Y. Yamazaki Y. Ren Y. Davis M.D. Liu C.C. Lu W. Wang X. Chen K. Cherukuri Y. APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer’s disease patient iPSC-derived cerebral organoids Nat. Commun. 2020 11 5540 10.1038/s41467-020-19264-0 33139712 PMC7608683 · DOI · Paper page
  20. [31]Lee S.I. Jeong W. Lim H. Cho S. Lee H. Jang Y. Cho J. Bae S. Lin Y.T. Tsai L.H. APOE4-carrying human astrocytes oversupply cholesterol to promote neuronal lipid raft expansion and Aβ generation Stem Cell Rep. 2021 16 2128 2137 10.1016/j.stemcr.2021.07.017 PMC8452535 34450034 · DOI · Paper page
  21. [32]Li N.M. Liu K.F. Qiu Y.J. Zhang H.H. Nakanishi H. Qing H. Mutations of beta-amyloid precursor protein alter the consequence of Alzheimer’s disease pathogenesis Neural Regen. Res. 2019 14 658 665 30632506 PMC6352587
  22. [33]Selkoe D.J. Presenilin, Notch, and the genesis and treatment of Alzheimer’s disease Proc. Natl. Acad. Sci. USA 2001 98 11039 11041 10.1073/pnas.211352598 11572965 PMC58679 · DOI
  23. [34]Weggen S. Beher D. Molecular consequences of amyloid precursor protein and presenilin mutations causing autosomal-dominant Alzheimer’s disease Alzheimers Res. Ther. 2012 4 9 10.1186/alzrt107 22494386 PMC3334542 · DOI · Paper page
  24. [36]Sarasija S. Laboy J.T. Ashkavand Z. Bonner J. Tang Y. Norman K.R. Presenilin mutations deregulate mitochondrial Ca Elife 2018 7 e33052 10.7554/eLife.33052 29989545 PMC6075864 · DOI
  25. [37]Walter P. Blobel G. Translocation of proteins across the endoplasmic reticulum III. Signal recognition protein (SRP) causes signal sequence-dependent and site-specific arrest of chain elongation that is released by microsomal membranes J. Cell Biol. 1981 91 Pt 1 557 561 10.1083/jcb.91.2.557 7309797 PMC2111983 · DOI
  26. [38]Kellogg M.K. Miller S.C. Tikhonova E.B. Karamyshev A.L. SRPassing Co-translational Targeting: The Role of the Signal Recognition Particle in Protein Targeting and mRNA Protection Int. J. Mol. Sci. 2021 22 6284 10.3390/ijms22126284 34208095 PMC8230904 · DOI
  27. [39]Kellogg M.K. Tikhonova E.B. Karamyshev A.L. Signal Recognition Particle in Human Diseases Front. Genet. 2022 13 898083 10.3389/fgene.2022.898083 35754847 PMC9214365 · DOI
  28. [40]von Heijne G. Signal sequences. The limits of variation J. Mol. Biol. 1985 184 99 105 10.1016/0022-2836(85)90046-4 4032478 · DOI
  29. [41]von Heijne G. Analysis of the distribution of charged residues in the N-terminal region of signal sequences: Implications for protein export in prokaryotic and eukaryotic cells EMBO J. 1984 3 2315 2318 10.1002/j.1460-2075.1984.tb02132.x 6499832 PMC557686 · DOI
  30. [42]von Heijne G. Protein targeting signals Curr. Opin. Cell Biol. 1990 2 604 608 10.1016/0955-0674(90)90100-S 2252586 · DOI
  31. [43]Nilsson I. Lara P. Hessa T. Johnson A.E. von Heijne G. Karamyshev A.L. The code for directing proteins for translocation across ER membrane: SRP cotranslationally recognizes specific features of a signal sequence J. Mol. Biol. 2015 427 Pt A 1191 1201 10.1016/j.jmb.2014.06.014 24979680 PMC4277940 · DOI
  32. [44]Karamyshev A.L. Patrick A.E. Karamysheva Z.N. Griesemer D.S. Hudson H. Tjon-Kon-Sang S. Nilsson I. Otto H. Liu Q. Rospert S. Inefficient SRP interaction with a nascent chain triggers a mRNA quality control pathway Cell 2014 156 146 157 10.1016/j.cell.2013.12.017 24439374 PMC3931426 · DOI
  33. [45]Karamyshev A.L. Tikhonova E.B. Karamysheva Z.N. Translational Control of Secretory Proteins in Health and Disease Int. J. Mol. Sci. 2020 21 2538 10.3390/ijms21072538 32268488 PMC7177344 · DOI
  34. [46]Tikhonova E.B. Karamysheva Z.N. von Heijne G. Karamyshev A.L. Silencing of Aberrant Secretory Protein Expression by Disease-Associated Mutations J. Mol. Biol. 2019 431 2567 2580 10.1016/j.jmb.2019.05.011 31100385 PMC6684239 · DOI
  35. [47]Karamyshev A.L. Karamysheva Z.N. Lost in Translation: Ribosome-Associated mRNA and Protein Quality Controls Front. Genet. 2018 9 431 10.3389/fgene.2018.00431 30337940 PMC6180196 · DOI
  36. [48]Karamysheva Z.N. Karamyshev A.L. Aberrant protein targeting activates quality control on the ribosome Front. Cell Dev. Biol. 2023 11 1198184 10.3389/fcell.2023.1198184 37346176 PMC10279951 · DOI
  37. [49]Pinarbasi E.S. Karamyshev A.L. Tikhonova E.B. Wu I.H. Hudson H. Thomas P.J. Pathogenic Signal Sequence Mutations in Progranulin Disrupt SRP Interactions Required for mRNA Stability Cell Rep. 2018 23 2844 2851 10.1016/j.celrep.2018.05.003 29874572 PMC6097231 · DOI
  38. [50]Karamysheva Z.N. Tikhonova E.B. Karamyshev A.L. Granulin in Frontotemporal Lobar Degeneration: Molecular Mechanisms of the Disease Front. Neurosci. 2019 13 395 10.3389/fnins.2019.00395 31105517 PMC6494926 · DOI
  39. [51]Hernandez S.M. Tikhonova E.B. Baca K.R. Zhao F. Zhu X. Karamyshev A.L. Unexpected Implication of SRP and AGO2 in Parkinson’s Disease: Involvement in Alpha-Synuclein Biogenesis Cells 2021 10 2792 10.3390/cells10102792 34685771 PMC8534902 · DOI
  40. [52]Tikhonova E.B. Gutierrez Guarnizo S.A. Kellogg M.K. Karamyshev A. Dozmorov I.M. Karamysheva Z.N. Karamyshev A.L. Defective Human SRP Induces Protein Quality Control and Triggers Stress Response J. Mol. Biol. 2022 434 167832 10.1016/j.jmb.2022.167832 36210597 PMC10024925 · DOI
  41. [53]Gadhave K. The signal peptide of the amyloid precursor protein forms amyloid-like aggregates and enhances Ab42 aggregation Cell Rep. Phys. Sci. 2021 2 100599 10.1016/j.xcrp.2021.100599 · DOI
  42. [54]Selkoe D.J. Alzheimer’s disease: Genes, proteins, and therapy Physiol. Rev. 2001 81 741 766 10.1152/physrev.2001.81.2.741 11274343 · DOI · Paper page
  43. [55]Rimal S. Li Y. Vartak R. Geng J. Tantray I. Li S. Huh S. Vogel H. Glabe C. Grinberg L.T. Inefficient quality control of ribosome stalling during APP synthesis generates CAT-tailed species that precipitate hallmarks of Alzheimer’s disease Acta Neuropathol. Commun. 2021 9 169 10.1186/s40478-021-01268-6 34663454 PMC8522249 · DOI
  44. [56]Simon S.M. Blobel G. A protein-conducting channel in the endoplasmic reticulum Cell 1991 65 371 380 10.1016/0092-8674(91)90455-8 1902142 · DOI
  45. [57]Rapoport T.A. Protein transport across the endoplasmic reticulum membrane FEBS J. 2008 275 4471 4478 10.1111/j.1742-4658.2008.06588.x 18671729 · DOI
  46. [58]Ast T. Cohen G. Schuldiner M. A network of cytosolic factors targets SRP-independent proteins to the endoplasmic reticulum Cell 2013 152 1134 1145 10.1016/j.cell.2013.02.003 23452858 · DOI
  47. [59]Liaci A.M. Förster F. Take Me Home, Protein Roads: Structural Insights into Signal Peptide Interactions during ER Translocation Int. J. Mol. Sci. 2021 22 11871 10.3390/ijms222111871 34769302 PMC8584900 · DOI
  48. [60]Goldgaber D. Lerman M.I. McBride O.W. Saffiotti U. Gajdusek D.C. Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer’s disease Science 1987 235 877 880 10.1126/science.3810169 3810169 · DOI
  49. [61]Yoshikai S. Sasaki H. Doh-ura K. Furuya H. Sakaki Y. Genomic organization of the human amyloid beta-protein precursor gene Gene 1990 87 257 263 10.1016/0378-1119(90)90310-N 2110105 · DOI
  50. [62]Lamb B.T. Sisodia S.S. Lawler A.M. Slunt H.H. Kitt C.A. Kearns W.G. Pearson P.L. Price D.L. Gearhart J.D. Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice [corrected] Nat. Genet. 1993 5 22 30 10.1038/ng0993-22 8220418 · DOI · Paper page
  51. [63]Delvaux E. Bentley K. Stubbs V. Sabbagh M. Coleman P.D. Differential processing of amyloid precursor protein in brain and in peripheral blood leukocytes Neurobiol. Aging 2013 34 1680 1686 10.1016/j.neurobiolaging.2012.12.004 23298733 PMC3598628 · DOI · Paper page
  52. [64]Kang J. Müller-Hill B. Differential splicing of Alzheimer’s disease amyloid A4 precursor RNA in rat tissues: PreA4(695) mRNA is predominantly produced in rat and human brain Biochem. Biophys. Res. Commun. 1990 166 1192 1200 10.1016/0006-291X(90)90992-V 1689572 · DOI
  53. [65]Korte M. Herrmann U. Zhang X. Draguhn A. The role of APP and APLP for synaptic transmission, plasticity, and network function: Lessons from genetic mouse models Exp. Brain Res. 2012 217 435 440 10.1007/s00221-011-2894-6 22006270 · DOI
  54. [66]Soba P. Eggert S. Wagner K. Zentgraf H. Siehl K. Kreger S. Löwer A. Langer A. Merdes G. Paro R. Homo- and heterodimerization of APP family members promotes intercellular adhesion EMBO J. 2005 24 3624 3634 10.1038/sj.emboj.7600824 16193067 PMC1276707 · DOI
  55. [67]Yamazaki T. Koo E.H. Selkoe D.J. Cell surface amyloid beta-protein precursor colocalizes with beta 1 integrins at substrate contact sites in neural cells J. Neurosci. 1997 17 1004 1010 10.1523/JNEUROSCI.17-03-01004.1997 8994055 PMC6573178 · DOI
  56. [68]Senechal Y. Kelly P.H. Dev K.K. Amyloid precursor protein knockout mice show age-dependent deficits in passive avoidance learning Behav. Brain Res. 2008 186 126 132 10.1016/j.bbr.2007.08.003 17884188 · DOI
  57. [69]White A.R. Reyes R. Mercer J.F. Camakaris J. Zheng H. Bush A.I. Multhaup G. Beyreuther K. Masters C.L. Cappai R. Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice Brain Res. 1999 842 439 444 10.1016/S0006-8993(99)01861-2 10526140 · DOI
  58. [70]Zhang X. Zhong W. Brankačk J. Weyer S.W. Müller U.C. Tort A.B. Draguhn A. Impaired theta-gamma coupling in APP-deficient mice Sci. Rep. 2016 6 21948 10.1038/srep21948 26905287 PMC4764939 · DOI
  59. [71]Young-Pearse T.L. Chen A.C. Chang R. Marquez C. Selkoe D.J. Secreted APP regulates the function of full-length APP in neurite outgrowth through interaction with integrin beta1 Neural Dev. 2008 3 15 10.1186/1749-8104-3-15 18573216 PMC2442059 · DOI · Paper page
  60. [73]Ring S. Weyer S.W. Kilian S.B. Waldron E. Pietrzik C.U. Filippov M.A. Herms J. Buchholz C. Eckman C.B. Korte M. The secreted beta-amyloid precursor protein ectodomain APPs alpha is sufficient to rescue the anatomical, behavioral, and electrophysiological abnormalities of APP-deficient mice J. Neurosci. 2007 27 7817 7826 10.1523/JNEUROSCI.1026-07.2007 17634375 PMC6672885 · DOI · Paper page
  61. [74]Farzan M. Schnitzler C.E. Vasilieva N. Leung D. Choe H. BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein Proc. Natl. Acad. Sci. USA 2000 97 9712 9717 10.1073/pnas.160115697 10931940 PMC16930 · DOI
  62. [75]Laird F.M. Cai H. Savonenko A.V. Farah M.H. He K. Melnikova T. Wen H. Chiang H.C. Xu G. Koliatsos V.E. BACE1, a major determinant of selective vulnerability of the brain to amyloid-beta amyloidogenesis, is essential for cognitive, emotional, and synaptic functions J. Neurosci. 2005 25 11693 11709 10.1523/JNEUROSCI.2766-05.2005 16354928 PMC2564291 · DOI · Paper page
  63. [76]Ohno M. Chang L. Tseng W. Oakley H. Citron M. Klein W.L. Vassar R. Disterhoft J.F. Temporal memory deficits in Alzheimer’s mouse models: Rescue by genetic deletion of BACE1 Eur. J. Neurosci. 2006 23 251 260 10.1111/j.1460-9568.2005.04551.x 16420434 · DOI · Paper page
  64. [77]Ohno M. Sametsky E.A. Younkin L.H. Oakley H. Younkin S.G. Citron M. Vassar R. Disterhoft J.F. BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer’s disease Neuron 2004 41 27 33 10.1016/S0896-6273(03)00810-9 14715132 · DOI · Paper page
  65. [78]Araki W. Post-translational regulation of the β-secretase BACE1 Brain Res. Bull. 2016 126 Pt 2 170 177 10.1016/j.brainresbull.2016.04.009 27086128 · DOI
  66. [79]Andrew R.J. Fernandez C.G. Stanley M. Jiang H. Nguyen P. Rice R.C. Buggia-Prévot V. De Rossi P. Vetrivel K.S. Lamb R. Lack of BACE1 S-palmitoylation reduces amyloid burden and mitigates memory deficits in transgenic mouse models of Alzheimer’s disease Proc. Natl. Acad. Sci. USA 2017 114 E9665 E9674 10.1073/pnas.1708568114 29078331 PMC5692556 · DOI
  67. [80]Huse J.T. Liu K. Pijak D.S. Carlin D. Lee V.M. Doms R.W. Beta-secretase processing in the trans-Golgi network preferentially generates truncated amyloid species that accumulate in Alzheimer’s disease brain J. Biol. Chem. 2002 277 16278 16284 10.1074/jbc.M111141200 11847218 · DOI
  68. [81]Schneider A. Rajendran L. Honsho M. Gralle M. Donnert G. Wouters F. Hell S.W. Simons M. Flotillin-dependent clustering of the amyloid precursor protein regulates its endocytosis and amyloidogenic processing in neurons J. Neurosci. 2008 28 2874 2882 10.1523/JNEUROSCI.5345-07.2008 18337418 PMC6670660 · DOI
  69. [82]Sannerud R. Declerck I. Peric A. Raemaekers T. Menendez G. Zhou L. Veerle B. Coen K. Munck S. De Strooper B. ADP ribosylation factor 6 (ARF6) controls amyloid precursor protein (APP) processing by mediating the endosomal sorting of BACE1 Proc. Natl. Acad. Sci. USA 2011 108 E559 E568 10.1073/pnas.1100745108 21825135 PMC3161548 · DOI
  70. [83]Sakurai T. Kaneko K. Okuno M. Wada K. Kashiyama T. Shimizu H. Akagi T. Hashikawa T. Nukina N. Membrane microdomain switching: A regulatory mechanism of amyloid precursor protein processing J. Cell Biol. 2008 183 339 352 10.1083/jcb.200804075 18936252 PMC2568028 · DOI
  71. [84]Bukhari H. Glotzbach A. Kolbe K. Leonhardt G. Loosse C. Müller T. Small things matter: Implications of APP intracellular domain AICD nuclear signaling in the progression and pathogenesis of Alzheimer’s disease Prog. Neurobiol. 2017 156 189 213 10.1016/j.pneurobio.2017.05.005 28587768 · DOI
  72. [85]Greenwood E.K. Angelova D.M. Büchner H.M.I. Brown D.R. The AICD fragment of APP initiates a FoxO3a mediated response via FANCD2 Mol. Cell. Neurosci. 2022 122 103760 10.1016/j.mcn.2022.103760 35901928 · DOI
  73. [86]Zhou D. Noviello C. D’Ambrosio C. Scaloni A. D’Adamio L. Growth factor receptor-bound protein 2 interaction with the tyrosine-phosphorylated tail of amyloid beta precursor protein is mediated by its Src homology 2 domain J. Biol. Chem. 2004 279 25374 25380 10.1074/jbc.M400488200 15054097 · DOI
  74. [87]Chen W.J. Goldstein J.L. Brown M.S. NPXY, a sequence often found in cytoplasmic tails, is required for coated pit-mediated internalization of the low density lipoprotein receptor J. Biol. Chem. 1990 265 3116 3123 10.1016/S0021-9258(19)39742-X 1968060 · DOI
  75. [88]Vieira S.I. Rebelo S. Domingues S.C. da Cruz e Silva E.F. da Cruz e Silva O.A. S655 phosphorylation enhances APP secretory traffic Mol. Cell. Biochem. 2009 328 145 154 10.1007/s11010-009-0084-7 19381782 · DOI
  76. [89]Vieira S.I. Rebelo S. Esselmann H. Wiltfang J. Lah J. Lane R. Small S.A. Gandy S. da Cruz e Silva E.F. da Cruz e Silva O.A. Retrieval of the Alzheimer’s amyloid precursor protein from the endosome to the TGN is S655 phosphorylation state-dependent and retromer-mediated Mol. Neurodegener. 2010 5 40 10.1186/1750-1326-5-40 20937087 PMC2994555 · DOI
  77. [90]Jiang S. Li Y. Zhang X. Bu G. Xu H. Zhang Y.W. Trafficking regulation of proteins in Alzheimer’s disease Mol. Neurodegener. 2014 9 6 10.1186/1750-1326-9-6 24410826 PMC3891995 · DOI
  78. [91]Lee M.S. Kao S.C. Lemere C.A. Xia W. Tseng H.C. Zhou Y. Neve R. Ahlijanian M.K. Tsai L.H. APP processing is regulated by cytoplasmic phosphorylation J. Cell Biol. 2003 163 83 95 10.1083/jcb.200301115 14557249 PMC2173445 · DOI
  79. [92]Suzuki T. Nakaya T. Regulation of amyloid beta-protein precursor by phosphorylation and protein interactions J. Biol. Chem. 2008 283 29633 29637 10.1074/jbc.R800003200 18650433 PMC2662050 · DOI
  80. [93]De Strooper B. Aph-1, Pen-2, and Nicastrin with Presenilin generate an active gamma-Secretase complex Neuron 2003 38 9 12 10.1016/S0896-6273(03)00205-8 12691659 · DOI · Paper page
  81. [94]Krishnaswamy S. Verdile G. Groth D. Kanyenda L. Martins R.N. The structure and function of Alzheimer’s gamma secretase enzyme complex Crit. Rev. Clin. Lab. Sci. 2009 46 282 301 10.3109/10408360903335821 19958215 · DOI
  82. [95]Haapasalo A. Kovacs D.M. The many substrates of presenilin/γ-secretase J. Alzheimers Dis. 2011 25 3 28 10.3233/JAD-2011-101065 21335653 PMC3281584 · DOI
  83. [96]Beel A.J. Sanders C.R. Substrate specificity of gamma-secretase and other intramembrane proteases Cell. Mol. Life Sci. 2008 65 1311 1334 10.1007/s00018-008-7462-2 18239854 PMC2569971 · DOI
  84. [97]Kanatsu K. Tomita T. Membrane trafficking and proteolytic activity of γ-secretase in Alzheimer’s disease Biol. Chem. 2016 397 827 835 10.1515/hsz-2016-0146 27390881 · DOI
  85. [99]Sisodia S.S. Beta-amyloid precursor protein cleavage by a membrane-bound protease Proc. Natl. Acad. Sci. USA 1992 89 6075 6079 10.1073/pnas.89.13.6075 1631093 PMC49440 · DOI
  86. [100]Carey R.M. Balcz B.A. Lopez-Coviella I. Slack B.E. Inhibition of dynamin-dependent endocytosis increases shedding of the amyloid precursor protein ectodomain and reduces generation of amyloid beta protein BMC Cell Biol. 2005 6 30 10.1186/1471-2121-6-30 16095541 PMC1208872 · DOI
  87. [101]Goodger Z.V. Rajendran L. Trutzel A. Kohli B.M. Nitsch R.M. Konietzko U. Nuclear signaling by the APP intracellular domain occurs predominantly through the amyloidogenic processing pathway J. Cell Sci. 2009 122 Pt 20 3703 3714 10.1242/jcs.048090 19773363 · DOI
  88. [102]Campioni S. Mannini B. Zampagni M. Pensalfini A. Parrini C. Evangelisti E. Relini A. Stefani M. Dobson C.M. Cecchi C. A causative link between the structure of aberrant protein oligomers and their toxicity Nat. Chem. Biol. 2010 6 140 147 10.1038/nchembio.283 20081829 · DOI
  89. [103]Fitzpatrick A.W. Debelouchina G.T. Bayro M.J. Clare D.K. Caporini M.A. Bajaj V.S. Jaroniec C.P. Wang L. Ladizhansky V. Müller S.A. Atomic structure and hierarchical assembly of a cross-β amyloid fibril Proc. Natl. Acad. Sci. USA 2013 110 5468 5473 10.1073/pnas.1219476110 23513222 PMC3619355 · DOI
  90. [104]Gu L. Liu C. Guo Z. Structural insights into Aβ42 oligomers using site-directed spin labeling J. Biol. Chem. 2013 288 18673 18683 10.1074/jbc.M113.457739 23687299 PMC3696641 · DOI
  91. [105]Sawaya M.R. Sambashivan S. Nelson R. Ivanova M.I. Sievers S.A. Apostol M.I. Thompson M.J. Balbirnie M. Wiltzius J.J. McFarlane H.T. Atomic structures of amyloid cross-beta spines reveal varied steric zippers Nature 2007 447 453 457 10.1038/nature05695 17468747 · DOI
  92. [106]Scheidt H.A. Morgado I. Rothemund S. Huster D. Dynamics of amyloid β fibrils revealed by solid-state NMR J. Biol. Chem. 2012 287 2017 2021 10.1074/jbc.M111.308619 22130659 PMC3265881 · DOI
  93. [107]Eisenberg D. Jucker M. The amyloid state of proteins in human diseases Cell 2012 148 1188 1203 10.1016/j.cell.2012.02.022 22424229 PMC3353745 · DOI
  94. [108]Chen J. Armstrong A.H. Koehler A.N. Hecht M.H. Small molecule microarrays enable the discovery of compounds that bind the Alzheimer’s Aβ peptide and reduce its cytotoxicity J. Am. Chem. Soc. 2010 132 17015 17022 10.1021/ja107552s 21062056 PMC3063105 · DOI
  95. [109]Zhang C. Liu Y. Gilthorpe J. van der Maarel J.R. MRP14 (S100A9) protein interacts with Alzheimer beta-amyloid peptide and induces its fibrillization PLoS ONE 2012 7 e32953 10.1371/journal.pone.0032953 22457725 PMC3310843 · DOI
  96. [110]Camandola S. Mattson M.P. Aberrant subcellular neuronal calcium regulation in aging and Alzheimer’s disease Biochim. Biophys. Acta 2011 1813 965 973 10.1016/j.bbamcr.2010.10.005 20950656 PMC3032815 · DOI
  97. [111]Demuro A. Smith M. Parker I. Single-channel Ca(2+) imaging implicates Aβ1-42 amyloid pores in Alzheimer’s disease pathology J. Cell Biol. 2011 195 515 524 10.1083/jcb.201104133 22024165 PMC3206345 · DOI
  98. [113]Moon H.E. Paek S.H. Mitochondrial Dysfunction in Parkinson’s Disease Exp. Neurobiol. 2015 24 103 116 10.5607/en.2015.24.2.103 26113789 PMC4479806 · DOI · Paper page
  99. [114]Anandatheerthavarada H.K. Biswas G. Mullick J. Sepuri N.B. Otvos L. Pain D. Avadhani N.G. Dual targeting of cytochrome P4502B1 to endoplasmic reticulum and mitochondria involves a novel signal activation by cyclic AMP-dependent phosphorylation at ser128 EMBO J. 1999 18 5494 5504 10.1093/emboj/18.20.5494 10523294 PMC1171618 · DOI
  100. [115]Robin M.A. Anandatheerthavarada H.K. Biswas G. Sepuri N.B. Gordon D.M. Pain D. Avadhani N.G. Bimodal targeting of microsomal CYP2E1 to mitochondria through activation of an N-terminal chimeric signal by cAMP-mediated phosphorylation J. Biol. Chem. 2002 277 40583 40593 10.1074/jbc.M203292200 12191992 PMC3800117 · DOI
  101. [117]Vaillant-Beuchot L. Mary A. Pardossi-Piquard R. Bourgeois A. Lauritzen I. Eysert F. Kinoshita P.F. Cazareth J. Badot C. Fragaki K. Accumulation of amyloid precursor protein C-terminal fragments triggers mitochondrial structure, function, and mitophagy defects in Alzheimer’s disease models and human brains Acta Neuropathol. 2021 141 39 65 10.1007/s00401-020-02234-7 33079262 PMC7785558 · DOI · Paper page
  102. [118]Mossmann D. Vögtle F.N. Taskin A.A. Teixeira P.F. Ring J. Burkhart J.M. Burger N. Pinho C.M. Tadic J. Loreth D. Amyloid-β peptide induces mitochondrial dysfunction by inhibition of preprotein maturation Cell Metab. 2014 20 662 669 10.1016/j.cmet.2014.07.024 25176146 · DOI
  103. [119]Sorrentino V. Romani M. Mouchiroud L. Beck J.S. Zhang H. D’Amico D. Moullan N. Potenza F. Schmid A.W. Rietsch S. Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity Nature 2017 552 187 193 10.1038/nature25143 29211722 PMC5730497 · DOI · Paper page
  104. [120]Calvo-Rodriguez M. Bacskai B.J. Mitochondria and Calcium in Alzheimer’s Disease: From Cell Signaling to Neuronal Cell Death Trends Neurosci. 2021 44 136 151 10.1016/j.tins.2020.10.004 33160650 · DOI · Paper page
  105. [121]Strope T.A. Wilkins H.M. Amyloid precursor protein and mitochondria Curr. Opin. Neurobiol. 2023 78 102651 10.1016/j.conb.2022.102651 36462447 PMC9845182 · DOI
  106. [122]Lykhmus O. Koval L. Voytenko L. Uspenska K. Komisarenko S. Deryabina O. Shuvalova N. Kordium V. Ustymenko A. Kyryk V. Intravenously Injected Mesenchymal Stem Cells Penetrate the Brain and Treat Inflammation-Induced Brain Damage and Memory Impairment in Mice Front. Pharmacol. 2019 10 355 10.3389/fphar.2019.00355 31057400 PMC6479176 · DOI
  107. [123]Xu F. Wu Y. Yang Q. Cheng Y. Xu J. Zhang Y. Dai H. Wang B. Ma Q. Chen Y. Engineered Extracellular Vesicles with SHP2 High Expression Promote Mitophagy for Alzheimer’s Disease Treatment Adv. Mater. 2022 34 e2207107 10.1002/adma.202207107 36193769 · DOI
  108. [124]Yin T. Liu Y. Ji W. Zhuang J. Chen X. Gong B. Chu J. Liang W. Gao J. Yin Y. Engineered mesenchymal stem cell-derived extracellular vesicles: A state-of-the-art multifunctional weapon against Alzheimer’s disease Theranostics 2023 13 1264 1285 10.7150/thno.81860 36923533 PMC10008732 · DOI
  109. [125]Vamecq J. Latruffe N. Medical significance of peroxisome proliferator-activated receptors Lancet 1999 354 141 148 10.1016/S0140-6736(98)10364-1 10408502 · DOI
  110. [126]Luo R. Su L.Y. Li G. Yang J. Liu Q. Yang L.X. Zhang D.F. Zhou H. Xu M. Fan Y. Activation of PPARA-mediated autophagy reduces Alzheimer disease-like pathology and cognitive decline in a murine model Autophagy 2020 16 52 69 10.1080/15548627.2019.1596488 30898012 PMC6984507 · DOI · Paper page
  111. [127]Sastre M. Dewachter I. Rossner S. Bogdanovic N. Rosen E. Borghgraef P. Evert B.O. Dumitrescu-Ozimek L. Thal D.R. Landreth G. Nonsteroidal anti-inflammatory drugs repress beta-secretase gene promoter activity by the activation of PPARgamma Proc. Natl. Acad. Sci. USA 2006 103 443 448 10.1073/pnas.0503839103 16407166 PMC1326151 · DOI · Paper page
  112. [128]Chen X.F. Zhang Y.W. Xu H. Bu G. Transcriptional regulation and its misregulation in Alzheimer’s disease Mol. Brain 2013 6 44 10.1186/1756-6606-6-44 24144318 PMC3854070 · DOI
  113. [129]Christensen M.A. Zhou W. Qing H. Lehman A. Philipsen S. Song W. Transcriptional regulation of BACE1, the beta-amyloid precursor protein beta-secretase, by Sp1 Mol. Cell. Biol. 2004 24 865 874 10.1128/MCB.24.2.865-874.2004 14701757 PMC343820 · DOI
  114. [130]Hirano F. Tanaka H. Hirano Y. Hiramoto M. Handa H. Makino I. Scheidereit C. Functional interference of Sp1 and NF-kappaB through the same DNA binding site Mol. Cell. Biol. 1998 18 1266 1274 10.1128/MCB.18.3.1266 9488441 PMC108839 · DOI
  115. [131]Rossello X.S. Igbavboa U. Weisman G.A. Sun G.Y. Wood W.G. AP-2β regulates amyloid beta-protein stimulation of apolipoprotein E transcription in astrocytes Brain Res. 2012 1444 87 95 10.1016/j.brainres.2012.01.017 22325097 PMC3292686 · DOI
  116. [132]Das H.K. Transcriptional regulation of the presenilin-1 gene: Implication in Alzheimer’s disease Front. Biosci. 2008 13 822 832 10.2741/2723 17981591 · DOI
  117. [133]Pastorcic M. Das H.K. Regulation of transcription of the human presenilin-1 gene by ets transcription factors and the p53 protooncogene J. Biol. Chem. 2000 275 34938 34945 10.1074/jbc.M005411200 10942770 · DOI
  118. [134]Pastorcic M. Das H.K. Analysis of transcriptional modulation of the presenilin 1 gene promoter by ZNF237, a candidate binding partner of the Ets transcription factor ERM Brain Res. 2007 1128 21 32 10.1016/j.brainres.2006.10.056 17126306 PMC1876729 · DOI
  119. [135]Hwang E.M. Kim S.K. Sohn J.H. Lee J.Y. Kim Y. Kim Y.S. Mook-Jung I. Furin is an endogenous regulator of alpha-secretase associated APP processing Biochem. Biophys. Res. Commun. 2006 349 654 659 10.1016/j.bbrc.2006.08.077 16942750 · DOI
  120. [136]Zhang Y. Bai X. Yao S. Cui Y. You L.H. Yu P. Chang Y.Z. Gao G. Hippocampal Iron Accumulation Impairs Synapses and Memory via Suppressing Furin Expression and Downregulating BDNF Maturation Mol. Neurobiol. 2022 59 5574 5590 10.1007/s12035-022-02929-w 35732869 · DOI
  121. [137]Beckelman B.C. Yang W. Kasica N.P. Zimmermann H.R. Zhou X. Keene C.D. Ryazanov A.G. Ma T. Genetic reduction of eEF2 kinase alleviates pathophysiology in Alzheimer’s disease model mice J. Clin. Investig. 2019 129 820 833 10.1172/JCI122954 30667373 PMC6355242 · DOI
  122. [138]Zhang N. Yu X. Xie J. Xu H. New Insights into the Role of Ferritin in Iron Homeostasis and Neurodegenerative Diseases Mol. Neurobiol. 2021 58 2812 2823 10.1007/s12035-020-02277-7 33507490 · DOI
  123. [139]Altamura S. Muckenthaler M.U. Iron toxicity in diseases of aging: Alzheimer’s disease, Parkinson’s disease and atherosclerosis J. Alzheimers Dis. 2009 16 879 895 10.3233/JAD-2009-1010 19387120 · DOI · Paper page
  124. [140]Rogers J.T. Randall J.D. Cahill C.M. Eder P.S. Huang X. Gunshin H. Leiter L. McPhee J. Sarang S.S. Utsuki T. An iron-responsive element type II in the 5′-untranslated region of the Alzheimer’s amyloid precursor protein transcript J. Biol. Chem. 2002 277 45518 45528 10.1074/jbc.M207435200 12198135 · DOI · Paper page
  125. [141]Hetz C. The unfolded protein response: Controlling cell fate decisions under ER stress and beyond Nat. Rev. Mol. Cell Biol. 2012 13 89 102 10.1038/nrm3270 22251901 · DOI
  126. [142]Cozachenco D. Ribeiro F.C. Ferreira S.T. Defective proteostasis in Alzheimer’s disease Ageing Res. Rev. 2023 85 101862 10.1016/j.arr.2023.101862 36693451 · DOI
  127. [143]Hosokawa N. Wada I. Hasegawa K. Yorihuzi T. Tremblay L.O. Herscovics A. Nagata K. A novel ER alpha-mannosidase-like protein accelerates ER-associated degradation EMBO Rep. 2001 2 415 422 10.1093/embo-reports/kve084 11375934 PMC1083879 · DOI
  128. [144]Nowakowska-Gołacka J. Czapiewska J. Sominka H. Sowa-Rogozińska N. Słomińska-Wojewódzka M. EDEM1 Regulates Amyloid Precursor Protein (APP) Metabolism and Amyloid-β Production Int. J. Mol. Sci. 2021 23 117 10.3390/ijms23010117 35008544 PMC8745108 · DOI
  129. [145]Joshi G. Wang Y. Golgi defects enhance APP amyloidogenic processing in Alzheimer’s disease Bioessays 2015 37 240 247 10.1002/bies.201400116 25546412 PMC4407201 · DOI
  130. [146]Joshi G. Chi Y. Huang Z. Wang Y. Aβ-induced Golgi fragmentation in Alzheimer’s disease enhances Aβ production Proc. Natl. Acad. Sci. USA 2014 111 E1230 E1239 10.1073/pnas.1320192111 24639524 PMC3977293 · DOI
  131. [147]Teunissen C.E. Verberk I.M.W. Thijssen E.H. Vermunt L. Hansson O. Zetterberg H. van der Flier W.M. Mielke M.M. Del Campo M. Blood-based biomarkers for Alzheimer’s disease: Towards clinical implementation Lancet Neurol. 2022 21 66 77 10.1016/S1474-4422(21)00361-6 34838239 · DOI · Paper page
  132. [148]Hansson O. Biomarkers for neurodegenerative diseases Nat. Med. 2021 27 954 963 10.1038/s41591-021-01382-x 34083813 · DOI · Paper page
  133. [150]Söderberg L. Johannesson M. Nygren P. Laudon H. Eriksson F. Osswald G. Möller C. Lannfelt L. Lecanemab, Aducanumab, and Gantenerumab—Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease Neurotherapeutics 2023 20 195 206 10.1007/s13311-022-01308-6 36253511 PMC10119362 · DOI
  134. [151]Jia Y. Cao N. Zhai J. Zeng Q. Zheng P. Su R. Liao T. Liu J. Pei H. Fan Z. HGF Mediates Clinical-Grade Human Umbilical Cord-Derived Mesenchymal Stem Cells Improved Functional Recovery in a Senescence-Accelerated Mouse Model of Alzheimer’s Disease Adv. Sci. 2020 7 1903809 10.1002/advs.201903809 32995116 PMC7507104 · DOI
  135. [152]Neves A.F. Camargo C. Premer C. Hare J.M. Baumel B.S. Pinto M. Intravenous administration of mesenchymal stem cells reduces Tau phosphorylation and inflammation in the 3xTg-AD mouse model of Alzheimer’s disease Exp. Neurol. 2021 341 113706 10.1016/j.expneurol.2021.113706 33757765 · DOI
  136. [153]Yang H. Yue C. Xie Z. Hu H. Wei L. Wang P. Zhao C. Bi J. Intravenous Administration of Human Umbilical Cord Mesenchymal Stem Cells Improves Cognitive Impairments and Reduces Amyloid-Beta Deposition in an AβPP/PS1 Transgenic Mouse Model Neurochem. Res. 2013 38 2474 2482 10.1007/s11064-013-1161-6 24078266 · DOI
  137. [154]Lim J.Y. In Park S. Park S.A. Jeon J.H. Jung H.Y. Yon J.M. Jeun S.S. Lim H.K. Kim S.W. Potential application of human neural crest-derived nasal turbinate stem cells for the treatment of neuropathology and impaired cognition in models of Alzheimer’s disease Stem Cell Res. Ther. 2021 12 402 10.1186/s13287-021-02489-1 34256823 PMC8278635 · DOI
  138. [155]Lim J.Y. Lee J.E. Park S.A. Park S.I. Yon J.M. Park J.A. Jeun S.S. Kim S.J. Lee H.J. Kim S.W. Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease Cells 2022 11 1029 10.3390/cells11061029 35326480 PMC8947560 · DOI
  139. [156]Zhang H.A. Yuan C.X. Liu K.F. Yang Q.F. Zhao J. Li H. Yang Q.H. Song D. Quan Z.Z. Qing H. Neural stem cell transplantation alleviates functional cognitive deficits in a mouse model of tauopathy Neural Regen. Res. 2022 17 152 162 34100451 PMC8451553
  140. [157]Chu J.J. Ji W.B. Zhuang J.H. Gong B.F. Chen X.H. Cheng W.B. Liang W.D. Li G.R. Gao J. Yin Y. Nanoparticles-based anti-aging treatment of Alzheimer’s disease Drug Deliv. 2022 29 2100 2116 10.1080/10717544.2022.2094501 35850622 PMC9302016 · DOI
  141. [158]Zhong G. Long H. Zhou T. Liu Y. Zhao J. Han J. Yang X. Yu Y. Chen F. Shi S. Blood-brain barrier Permeable nanoparticles for Alzheimer’s disease treatment by selective mitophagy of microglia Biomaterials 2022 288 121690 10.1016/j.biomaterials.2022.121690 35965114 · DOI

Cited by

Sorted by citations

Authors
Orobets, K. S., & Karamyshev, A. L.
Affiliations
Texas Tech University (US)
Corresponding author
Karamyshev, Andrey L.
ORCID
Karamyshev, Andrey L.
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2023-09-30
Volume
24
Issue
19
Pages
14794
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms241914794
PMC
PMC10573485
OpenAlex
W4387230982
Cited by
141
References
16
Citations by year
2026: 57 · 2025: 56 · 2024: 27 · 2023: 1
FWCI
4.73
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Center of Excellence for Translational Neuroscience and Therapeutics (CTNT) and the TTUHSC Office of Research (CTNT-OR 2022-04 AKMM)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, amyloid precursor protein, amyloid-beta, tau hyperphosphorylation, amyloidogenic pathway, non-amyloidogenic pathway, APP processing, amyloid plaques, synaptic loss, energy metabolism, metal homeostasis, antibody-based therapy, stem cell transplantation, dementia
MeSH terms
Alzheimer Disease, Humans, Membrane Proteins, Amyloid beta-Peptides, Amyloid beta-Protein Precursor

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review