CoChat
Sign Up
Cited by 33Autophagy in Disease and TherapyAlzheimer's disease research and treatmentsAmyotrophic Lateral Sclerosis Research

The role of lysosomes and autophagosomes in frontotemporal lobar degeneration

Open access
Bain, H. D. C., Davidson, Y. S., Robinson, A. C., Ryan, S., Rollinson, S., Richardson, A., Jones, M., Snowden, J. S. +2 more·2019·Neuropathology and Applied Neurobiology
DOI 10.1111/nan.12500PMC PMC6487817
Open this paper in CoChat — free accountOpen PDF

Abstract

Introduction: Cell biological and genetic evidence implicate failures in degrading aggregating proteins, such as tau and TDP‐43, through the autophagy or lysosomal pathways in the pathogenesis of frontotemporal lobar degeneration (FTLD). Methods: We investigated changes in the degradative pathways in 60 patients with different pathological or genetic forms of FTLD employing immunohistochemistry for marker proteins such as lysosomal‐associated membrane proteins 1 (LAMP‐1) and 2 (LAMP‐2), cathepsin D (CTSD) and microtubule‐associated protein 1 light chain 3 alpha (LC 3A). Immunostained sections were qualitatively and semi‐quantitatively assessed for the appearance, distribution and intensity of staining in neurones of the dentate gyrus (DG) and CA 4 region of the hippocampus, and the temporal cortex (Tcx). Results: Lower levels of neuronal LAMP‐1 immunostaining were present in the DG and Tcx in FTLD‐tau compared to FTLD‐TDP. There was less LAMP‐1 immunostaining in FTLD‐tau with MAPT mutations, and FTLD‐tau with Pick bodies, compared to FTLD‐TDP types A and B, and less LAMP‐1 immunostaining in FTLD‐TDP type C than in FTLD‐TDP types A and B. There was greater LAMP‐1 immunostaining in GRN mutation which may reflect the underlying type A histology rather than mutation. There were no differences in neuronal LAMP‐2, CTSD, EEA‐1 or LC 3A immunostaining between any of the five FTLD histological or four genetic groups, nor between FTLD‐TDP and FTLD‐tau. Conclusions: The underlying pathological mechanism in FTLD‐tau may lie with a relative deficiency of lysosomes, or defective vesicular transport, whereas the failure to clear TDP‐43 aggregates may lie with lysosomal dysfunction rather than a lack of available lysosomes or degradative enzymes.

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 · 10.1111/nan.12500

Cites

7 of 7 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?

  • Disruption of the autophagy-lysosomal pathway is a pathological hallmark in human tauopathy brain.

    “Disruption of the autophagy-lysosomal pathway (ALP) is another pathological hallmark in human tauopathy brain (Bain et al., 2019; Piras et al., 2016; Wang et al., 2009).”

    From ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids (2021) · cites this paper as Bain et al., 2019

    The Discussion reports lower LAMP-1 levels in human FTLD-tau cases and suggests that deficient lysosomes or defective vesicular transport may impair tau clearance. This supports disruption of the pathway in the FTLD-tau cases studied, but the paper does not establish it as a pathological hallmark across human tauopathies; its mechanistic conclusion is hedged. (LLM, conf=0.84)

    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: 51

  1. [1]Snowden JS, Neary D, Mann DMA. Frontotemporal dementia. Lancet Neurol 2005; 4: 771– 80 16239184
  2. [2]Saxon JA, Harris JM, Thompson JC, Jones M, Richardson AMT, Langheinrich T, Neary D, Mann DMA, Snowden JS. Semantic dementia, progressive non‐fluent aphasia and their association with amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2017; 88: 711– 712. 28554960 PMC5537533
  3. [3]Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden M, Pickering‐Brown SM, Chakraverty S, Isaacs A, Grover A, Hackett J, Adamson J, Lincoln S, Dickson D, Davies P, Petersen RC, Stevens M, de Graaf E, Wauters E, van Baren J, Hillebrand M, Joosse M, Kwon JM, Nowotny P, Che LK, Norton J, Morris JC, Reed LA, Trojanowski JQ, Basun H, Lannfelt L, Neystat M, Fahn S, Dark F, Tannenberg T, Dodd P, Hayward N, Kwok JBJ, Schofield PR, Andreadis A, Snowden J, Craufurd D, Neary D, Owen F, Oostra BA, Hardy J, Goate A, van Swieten J, Mann DM, Lynch T, Heutink P. Association of missense and 5'–splice‐site mutation in tau with inherited dementia FTDP‐17. Nature 1998; 393: 702– 5 9641683
  4. [5]Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H, Pirici D, Rademakers R, Vandenberghe R, Dermaut B, Martin JJ, van Duijn C, Peeters K, Sciot R, Santens P, De Pooter T, Mattheijssens M, Van den Broeck M, Cuijt I, Vennekens K, De Deyn PP, Kumar‐Singh S, Van Broeckhoven C. Null mutations in progranulin cause ubiquitin‐positive frontotemporal dementia linked to chromosome 17q21. Nature 2006; 442: 920– 4 16862115
  5. [6]DeJesus‐Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, Nicholson AM, Finch NA, Flynn H, Adamson J, Kouri N, Wojtas A, Sengdy P, Hsiung GY, Karydas A, Seeley WW, Josephs KA, Coppola G, Geschwind DH, Wszolek ZK, Feldman H, Knopman DS, Petersen RC, Miller BL, Dickson DW, Boylan KB, Graff‐Radford NR, Rademakers R. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p‐linked FTD and ALS. Neuron 2011; 72: 245– 56 21944778 PMC3202986
  6. [7]Renton AE, Majounie E, Waite A, Simón‐Sánchez J, Rollinson S, Gibbs JR, Laaksovirta H, Schymick JC, van Swieten J, Myllykangas L, Kalimo H, Paetau A, Abramzon Y, Remes AM, Kaganovich A, Scholz SW, Duckworth J, Ding J, Harmer DW, Hernandez DG, Johnson JO, Mok K, Ryten M, Trabzuni D, Guerreiro RJ, Orrell RW, Neal J, Murray A, Pearson J, Jansen IE, Sondervan D, Seelaar H, Blake D, Young K, Halliwell N, Callister J, Toulson G, Richardson A, Gerhard A, Snowden J, Mann D, Neary D, Nalls MA, Peuralinna T, Jansson L, Isoviita V‐M, Kaivorinne A‐L, Holtta‐Vuori M, Ikonen E, Sulkava R, Benatar M, Wuu J, Chio A, Restagno G, Borghero G, Sabatelli M; The ITALSGEN Consortium, Heckerman D, Rogaeva E, Zinman L, Rothstein J, Sendtner M, Drepper C, Eichler EE, Alkan C, Abdullaev Z, Pack SD, Dutra A, Pak E, Hardy J, Singleton A, Williams NM, Heutink P, Pickering‐Brown S, Morris HR, Tienari PJ, Traynor BJ. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21‐linked ALS‐FTD. Neuron 2011; 72: 257– 68. 21944779 PMC3200438
  7. [8]Watts GD, Wymer J, Kovach MJ, Mehta SG, Mumm S, Darvish D, Pestronk A, Whyte MP, Kimonis VE. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin‐containing protein. Nature Genet 2004; 36: 377– 81 15034582
  8. [10]Deng HX, Chen W, Hong ST, Boycott KM, Gorrie GH, Siddique N, Yang Y, Fecto F, Shi Y, Zhai H, Jiang H, Hirano M, Rampersaud E, Jansen GH, Donkervoort S, Bigio EH, Brooks BR, Ajroud K, Sufit RL, Haines JL, Mugnaini E, Pericak‐Vance MA, Siddique T. Mutations in UBQLN2 cause dominant X‐linked juvenile and adult‐onset ALS and ALS/dementia. Nature 2011; 477: 211– 5 21857683 PMC3169705
  9. [11]Maruyama H, Morino H, Ito H, Izumi Y, Kato H, Watanabe Y, Kinoshita Y, Kamada M, Nodera H, Suzuki H, Komure O, Matsuura S, Kobatake K, Morimoto N, Abe K, Suzuki N, Aoki M, Kawata A, Hirai T, Kato T, Ogasawara K, Hirano A, Takumi T, Kusaka H, Hagiwara K, Kaji R, Kawakami H. Mutations of optineurin in amyotrophic lateral sclerosis. Nature 2010; 465: 223– 6 20428114
  10. [12]Miller L, Rollinson S, Callister J, Young K, Harris J, Gerhard A, Richardson A, Jones M, Snowden J, Mann DMA, Pickering‐Brown SM. p62/SQSTM1 analysis in frontotemporal lobar degeneration. Neurobiol Aging 2015; 36: e5– 9 25433461
  11. [13]Van Deerlin VM, Sleiman PM, Martinez‐Lage M, Chen‐Plotkin A, Wang LS, Graff‐Radford NR, Dickson DW, Rademakers R, Boeve BF, Grossman M, Arnold SE, Mann DM, Pickering‐Brown SM, Seelaar H, Heutink P, van Swieten JC, Murrell JR, Ghetti B, Spina S, Grafman J, Hodges J, Spillantini MG, Gilman S, Lieberman AP, Kaye JA, Woltjer RL, Bigio EH, Mesulam M, Al‐Sarraj S, Troakes C, Rosenberg RN, White CL 3rd, Ferrer I, Lladó A, Neumann M, Kretzschmar HA, Hulette CM, Welsh‐Bohmer KA, Miller BL, Alzualde A, de Lopez Munain A, McKee AC, Gearing M, Levey AI, Lah JJ, Hardy J, Rohrer JD, Lashley T, Mackenzie IR, Feldman HH, Hamilton RL, Dekosky ST, der van Zee J, Kumar‐Singh S, Van Broeckhoven C, Mayeux R, Vonsattel JP, Troncoso JC, Kril JJ, Kwok JB, Halliday GM, Bird TD, Ince PG, Shaw PJ, Cairns NJ, Morris JC, McLean CA, DeCarli C, Ellis WG, Freeman SH, Frosch MP, Growdon JH, Perl DP, Sano M, Bennett DA, Schneider JA, Beach TG, Reiman EM, Woodruff BK, Cummings J, Vinters HV, Miller CA, Chui HC, Alafuzoff I, Hartikainen P, Seilhean D, Galasko D, Masliah E, Cotman CW, Tuñón MT, Martínez MC, Munoz DG, Carroll SL, Marson D, Riederer PF, Bogdanovic N, Schellenberg GD, Hakonarson H, Trojanowski JQ, Lee VM. Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP‐43 inclusions. Nat Genet 2010; 42: 234– 9 20154673 PMC2828525
  12. [14]Shi J, Shaw CL, Richardson AMT, Bailey K, Tian J, Varma AR, Neary D, Snowden JS, Mann DMA. Histopathological changes underlying frontotemporal lobar degeneration with clinicopathological correlation. Acta Neuropathol 2005; 110: 501– 12 16222525
  13. [15]Chakrabarti A, Chen AW, Varner JD. A review of the mammalian unfolded protein response. Biotechnol Bioeng 2011; 108: 2777– 93 21809331 PMC3193940
  14. [16]Kroemer G, Mariño G, Levine B. Autophagy and the integrated stress response. Mol Cell 2010; 40: 280– 93 20965422 PMC3127250
  15. [17]Kuzuhara S, Mori H, Izumiyama N, Yoshimura M, Ihara Y. Lewy bodies are ubiquitinated. Acta Neuropathol 1988; 75: 345– 53 3364159
  16. [18]Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 1998; 39: 605– 8 9560156
  17. [19]Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, Harta G, Brownstein MJ, Jonnalagada S, Chernova T, Dehejia A, Lavedan C, Gasser T, Steinbach PJ, Wilkinson KD, Polymeropoulos MH. The ubiquitin pathway in Parkinson's disease. Nature 1998; 395: 451– 2 9774100
  18. [20]McNaught K, Belizaire R, Isacson O, Jenner P, Olanow CW. Altered proteasomal function in sporadic Parkinson's disease. Expl Neurol 2003; 179: 38– 46 12504866
  19. [21]Bukhatwa S, Zeng B‐Y, Rose S, Jenner P. A comparison of changes in proteasomal subunit expression in the substantia nigra in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy. Brain Res 2010; 1326: 174– 83 20176003
  20. [22]Dai RM, Li CC. Valosin‐containing protein is a multi‐ubiquitin chain‐targeting factor required in ubiquitin‐proteasome degradation. Nat Cell Biol 2001; 3: 740– 4 11483959
  21. [23]Markovinovic A, Cimbro R, Ljutic T, Kriz J, Rogelj B, Munitic I. Optineurin in amyotrophic lateral sclerosis: multifunctional adaptor protein at the crossroads of different neuroprotective mechanisms. Prog Neurobiol 2017; 154: 1– 20 28456633
  22. [24]Kuusisto E, Salminen A, Alfuzoff I. Ubiquitin‐binding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies. NeuroReport 2001; 12: 2085– 90 11447312
  23. [26]Hu F, Padukkavidana T, Vægter CB, Brady OA, Zheng Y, Mackenzie IR, Feldman HH, Nykjaer A, Strittmatter SM. Sortilin‐mediated endocytosis determines levels of the frontotemporal dementia protein, progranulin. Neuron 2010; 68: 654– 67 21092856 PMC2990962
  24. [27]Zhou X, Sun L, Bastos de Oliveira F, Qi X, Brown WJ, Smolka MB, Sun Y, Hu F. Prosaposin facilitates sortilin‐independent lysosomal trafficking of progranulin. J Cell Biol 2015; 210: 991– 1002 26370502 PMC4576858
  25. [28]Sellier C, Campanari ML, Julie Corbier C, Gaucherot A, Kolb‐Cheynel I, Oulad‐Abdelghani M, Ruffenach F, Page A, Ciura S, Kabashi E, Charlet‐Berguerand N. Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin‐2 to induce motor neuron dysfunction and cell death. EMBO J 2016; 35: 1276– 97 27103069 PMC4910533
  26. [29]Sullivan PM, Zhou X, Robins AM, Paushter DH, Kim D, Smolka MB, Hu F. The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy‐lysosome pathway. Acta Neuropathol Commun 2016; 4: 5 27193190 PMC4870812
  27. [31]Smith KR, Damiano J, Franceschetti S, Carpenter S, Canafoglia L, Morbin M, Rossi G, Pareyson D, Mole SE, Staropoli JF, Sims KB, Lewis J, Lin WL, Dickson DW, Dahl HH, Bahlo M, Berkovic SF. Strikingly different clinicopathological phenotypes determined by progranulin‐mutation dosage. Am J Hum Genet 2012; 90: 1102– 7 22608501 PMC3370276
  28. [32]Almeida MR, Macário MC, Ramos L, Baldeiras I, Ribeiro MH, Santana I. Portuguese family with the co‐occurrence of frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis phenotypes due to progranulin gene mutation. Neurobiol Aging 2016; 41: e1– 200.e5 27021778
  29. [33]Götzl JK, Mori K, Damme M, Fellerer K, Tahirovic S, Kleinberger G, Janssens J, van der Zee J, Lang CM, Kremmer E, Martin JJ, Engelborghs S, Kretzschmar HA, Arzberger T, Van Broeckhoven C, Haass C, Capell A. Common pathobiochemical hallmarks of progranulin‐associated frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis. Acta Neuropathol 2014; 127: 845– 60 24619111
  30. [34]Zhou X, Paushter DH, Feng T, Pardon CM, Mendoza CS, Hu F. Regulation of cathepsin D activity by the FTLD protein progranulin. Acta Neuropathol 2017; 134: 151– 3 28493053 PMC5568051
  31. [35]Eskelinen E‐L. Roles of LAMP‐1 and LAMP‐2 in lysosome biogeneis and autophagy. Mol Aspects Med 2006; 27: 495– 502 16973206
  32. [36]Kaushik S, Cuervo AM. Chaperone‐mediated autophagy: a unique way to enter the lysosome world. Trend Cell Biol 2012; 22: 407– 17 PMC3408550 22748206
  33. [39]Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert PH, Albert M, Boone K, Miller BL, Cummings J, Benson DF. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998; 51: 1546– 54 9855500
  34. [40]Gorno‐Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, Ogar JM, Rohrer JD, Black S, Boeve BF, Manes F, Dronkers NF, Vandenberghe R, Rascovsky K, Patterson K, Miller BL, Knopman DS, Hodges JR, Mesulam MM, Grossman M. Classification of primary progressive aphasia and its variants. Neurology 2011; 76: 1006– 14 21325651 PMC3059138
  35. [41]Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC, Seelaar H, Dopper EG, Onyike CU, Hillis AE, Josephs KA, Boeve BF, Kertesz A, Seeley WW, Rankin KP, Johnson JK, Gorno‐Tempini ML, Rosen H, Prioleau‐Latham CE, Lee A, Kipps CM, Lillo P, Piguet O, Rohrer JD, Rossor MN, Warren JD, Fox NC, Galasko D, Salmon DP, Black SE, Mesulam M, Weintraub S, Dickerson BC, Diehl‐Schmid J, Pasquier F, Deramecourt V, Lebert F, Pijnenburg Y, Chow TW, Manes F, Grafman J, Cappa SF, Freedman M, Grossman M, Miller BL. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 2011; 134: 2456– 71 21810890 PMC3170532
  36. [42]Snowden JS, Thompson JC, Stopford CL, Richardson AMT, Gerhard A, Neary D, Mann DMA. The clinical diagnosis of early‐onset dementias: diagnostic accuracy and clinicopathological relationships. Brain 2012; 135: 693– 708 21840888
  37. [43]Thompson JC, Stopford CL, Snowden JS, Neary D. Qualitative neuropsychological performance characteristics in frontotemporal dementia and Alzheimer's disease. J Neurol Neurosurg Psychiatr 2005; 76: 920– 7 PMC1739700 15965196
  38. [44]Mackenzie IRA, Neumann M, Baborie A, Sampathu DM, Du Plessis D, Jaros E, Perry RH, Trojanowski JQ, Mann DMA, Lee VM‐Y. A harmonized classification system for FTLD‐TDP pathology. Acta Neuropathol 2011; 122: 111– 3 21644037 PMC3285143
  39. [45]Mann DMA, Rollinson S, Robinson A, Callister J, Snowden JS, Gendron T, Petrucelli L, Masuda‐Suzukake M, Hasegawa M, Davidson YS, Pickering‐Brown S. Dipeptide repeat proteins are present in the p62 positive inclusions in patients with frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9ORF72. Acta Neuropathol Comm 2013; 1: 68 PMC3893586 24252525
  40. [46]Davidson Y, Barker H, Robinson AC, Troakes C, Smith B, Al‐Sarraj S, Shaw C, Rollinson S, Masuda‐Suzukake M, Hasegawa M, Pickering‐Brown S, Snowden JS, Mann DMA. Brain distribution of dipeptide repeat proteins in frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9ORF72. Acta Neuropathol Comm 2014; 2: 70 PMC4229740 24950788
  41. [47]Sardiello M, Donaudy F, Embrione V, Polishchuk RS, Banfi S, Parenti G, Cattaneo E, Ballabio A. A gene network regulating lysosomal biogenesis and function. Science 2009; 325: 473– 7 19556463
  42. [48]Beel S, Moisse M, Damme M, De Muynck L, Robberecht W, Van Den Bosch L, Saftig P, Van Damme P. Progranulin functions as a cathepsin D chaperone to stimulate axonal outgrowth in vivo. Hum Mol Genet 2017; 26: 2850– 63 28453791 PMC5886064
  43. [49]Tanaka Y, Suzuki G, Matsuwaki T, Hosokawa M, Serrano G, Beach TG, Yamanouchi K, Hasegawa M, Nishihara M. Progranulin regulates lysosomal function and biogenesis through acidification of lysosomes. Hum Mol Genet 2017; 26: 969– 88 28073925
  44. [50]Simon D, García‐García E, Royo F, Falcón‐Pérez JM, Avila J. Proteostasis of tau. Tau overexpression results in its secretion via membrane vesicles. FEBS Lett 2012; 586: 527– 34 22138183
  45. [51]Lant SB, Robinson AC, Thompson JC, Rollinson S, Pickering‐Brown S, Snowden JS, Davidson YS, Gerhard A, Mann DM. Patterns of microglial cell activation in frontotemporal lobar degeneration. Neuropathol Appl Neurobiol 2014; 40: 686– 96 24117616
  46. [52]Polito VA, Li H, Martini‐Stoica H, Wang B, Yang L, Xu Y, Swartzlander DB, Palmieri M, di Ronza A, Lee VM, Sardiello M, Ballabio A, Zheng H. Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB. EMBO Mol Med 2014; 6: 1142– 60 25069841 PMC4197862
  47. [53]Kochl R, Hu XW, Chan EY, Tooze SA. Microtubules facilitate autophagosome formation and fusion of autophagosomes with endosomes. Traffic 2006; 7: 129– 45 16420522
  48. [55]Armstrong RA, Cairns NJ, Lantos PL. Clustering of Pick bodies in the dentate gyrus in Pick's disease. Neuropathology 2000; 20: 170– 5 11132931
  49. [56]Miki Y, Mori F, Tanji K, Kurotaki H, Kakita A, Takahashi H, Wakabayashi K. An autopsy case of incipient Pick's disease: immunohistochemical profile of early‐stage Pick body formation. Neuropathology 2014; 34: 386– 91 24444359
  50. [57]Odagiri S, Tanji K, Mori F, Kakita A, Takahashi H, Wakabayashi K. Autophagic adapter protein NBR1 is localised to Lewy bodies and glial cytoplasmic inclusions and is involved in aggregate formation in α‐synucleinopathy. Acta Neuropathol 2012; 124: 173– 86 22484440
  51. [58]Miki Y, Mori F, Tanji K, Kakita A, Takahashi H, Wakabayashi K. Accumulation of histone deacetylase 6, an aggresome‐related protein, is specific to Lewy bodies and glial cytoplasmic inclusions. Neuropathology 2011; 31: 561– 8 21284752

Cited by

Sorted by citations

Authors
Bain, H. D. C., Davidson, Y. S., Robinson, A. C., Ryan, S., Rollinson, S., Richardson, A., Jones, M., Snowden, J. S., Pickering‐Brown, S., & Mann, D. M. A.
Affiliations
  • University of Manchester (GB)
  • Salford Royal Hospital (GB)
  • Division of Neuroscience and Experimental Psychology School of Biological Sciences Faculty of Biology, Medicine and Health University of Manchester Manchester UK
Corresponding author
Mann, D. M. A.
ORCID
Venue
Neuropathology and Applied Neurobiology
Publisher
Wiley
Published
2018-06-19
Volume
45
Issue
3
Pages
244-261
ISSN
  • 0305-1846 (ISSN-L)
  • 1365-2990
DOI
10.1111/nan.12500
PMC
PMC6487817
OpenAlex
W2803867053
Cited by
33
References
7
Citations by year
2026: 1 · 2025: 5 · 2024: 1 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 9 · 2019: 2 · 2018: 2
FWCI
3.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuropathology and Applied Neurobiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion, cc-by)
Funders
Medical Research Council (G0701041)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
frontotemporal lobar degeneration, lysosomes, autophagy, autophagosomes, lysosomal dysfunction, TDP-43, LAMP1, LAMP2, cathepsin D, LC3A, GRN mutations, MAPT mutations, Pick bodies, protein aggregate clearance, dentate gyrus, hippocampus, temporal cortex
MeSH terms
Autophagosomes, Aged, Aged, 80 and over, Alzheimer Disease, Cathepsin D, Female, Humans, Lysosomes, Male, Microtubule-Associated Proteins, Middle Aged, Lysosomal Membrane Proteins, Lysosomal-Associated Membrane Protein 1, Lysosomal-Associated Membrane Protein 2, Frontotemporal Lobar Degeneration

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