Moving from neurodegenerative dementias, to cognitive proteinopathies, replacing “where” by “what”

Neurodegenerative dementias have been described based on their phenotype, in relation to selective degeneration occurring in a particular neuroanatomical system. More recently however, the term proteinopathy has been introduced to describe diseases in which one or more altered proteins can be detect...

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Autores:
Allegri, Ricardo Francisco
Tipo de recurso:
Article of journal
Fecha de publicación:
2020
Institución:
Corporación Universidad de la Costa
Repositorio:
REDICUC - Repositorio CUC
Idioma:
eng
OAI Identifier:
oai:repositorio.cuc.edu.co:11323/7992
Acceso en línea:
https://hdl.handle.net/11323/7992
https://doi.org/10.1590/1980-57642020dn14-030005
https://repositorio.cuc.edu.co/
Palabra clave:
Alzheimer disease
Proteins
Frontotemporal dementia
Biomarkers
Dementia
Rights
openAccess
License
CC0 1.0 Universal
id RCUC2_ff56947ae314a0931cf1fd4403ee5db4
oai_identifier_str oai:repositorio.cuc.edu.co:11323/7992
network_acronym_str RCUC2
network_name_str REDICUC - Repositorio CUC
repository_id_str
dc.title.spa.fl_str_mv Moving from neurodegenerative dementias, to cognitive proteinopathies, replacing “where” by “what”
title Moving from neurodegenerative dementias, to cognitive proteinopathies, replacing “where” by “what”
spellingShingle Moving from neurodegenerative dementias, to cognitive proteinopathies, replacing “where” by “what”
Alzheimer disease
Proteins
Frontotemporal dementia
Biomarkers
Dementia
title_short Moving from neurodegenerative dementias, to cognitive proteinopathies, replacing “where” by “what”
title_full Moving from neurodegenerative dementias, to cognitive proteinopathies, replacing “where” by “what”
title_fullStr Moving from neurodegenerative dementias, to cognitive proteinopathies, replacing “where” by “what”
title_full_unstemmed Moving from neurodegenerative dementias, to cognitive proteinopathies, replacing “where” by “what”
title_sort Moving from neurodegenerative dementias, to cognitive proteinopathies, replacing “where” by “what”
dc.creator.fl_str_mv Allegri, Ricardo Francisco
dc.contributor.author.none.fl_str_mv Allegri, Ricardo Francisco
dc.subject.spa.fl_str_mv Alzheimer disease
Proteins
Frontotemporal dementia
Biomarkers
Dementia
topic Alzheimer disease
Proteins
Frontotemporal dementia
Biomarkers
Dementia
description Neurodegenerative dementias have been described based on their phenotype, in relation to selective degeneration occurring in a particular neuroanatomical system. More recently however, the term proteinopathy has been introduced to describe diseases in which one or more altered proteins can be detected. Neurodegenerative diseases can be produced by more than one abnormal protein and each proteinopathy can determine different clinical phenotypes. Specific biomarkers have now been linked to certain molecular pathologies in live patients. In 2016, a new biomarker-based classification, currently only approved for research in Alzheimer’s disease, was introduced. It is based on the evaluation three biomarkers: amyloid (A) detected on amyloid-PET or amyloid- beta 42 assay in CSF; tau (T) measured in CSF as phosphorylated tau or on tau PET imaging; and neuronal injury/neurodegeneration (N), detected by total T-tau in CSF, FDG PET hypometabolism and on MRI brain scan. Results of clinical research using the ATN biomarkers at FLENI, a Neurological Institute in Buenos Aires, Argentina have, since 2011, contributed to ongoing efforts to move away from the concept of neurodegenerative dementias and more towards one of cognitive proteinopathies. Today, clinical diagnosis in dementia can only tell us “where” abnormal tissue is found but not “what” molecular mechanisms are involved
publishDate 2020
dc.date.issued.none.fl_str_mv 2020-09-18
dc.date.accessioned.none.fl_str_mv 2021-03-12T15:55:18Z
dc.date.available.none.fl_str_mv 2021-03-12T15:55:18Z
dc.type.spa.fl_str_mv Artículo de revista
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dc.identifier.doi.spa.fl_str_mv https://doi.org/10.1590/1980-57642020dn14-030005
dc.identifier.instname.spa.fl_str_mv Corporación Universidad de la Costa
dc.identifier.reponame.spa.fl_str_mv REDICUC - Repositorio CUC
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Corporación Universidad de la Costa
REDICUC - Repositorio CUC
url https://hdl.handle.net/11323/7992
https://doi.org/10.1590/1980-57642020dn14-030005
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dc.language.iso.none.fl_str_mv eng
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dc.relation.references.spa.fl_str_mv 1. Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012;367(9):795-804. 10.1056/NEJMoa1202753
2. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984;34(7):939-44. https://doi.org/10.1212/wnl.34.7.939
3. Mendez PC, Surace E, Bérgamo Y, Calandri I, Vázquez S, Sevlever G, et al. Biomarkers for Alzheimer's disease. Where we stand and where we are headed. Medicina (B Aires). 2019;79(Spec 6/1):546-51.
4. Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol. 2014;13(6):614-29. https://doi.org/10.1016/s1474-4422(14)70090-0
5. Allegri RF, Vazquez S, Sevlever G. Enfermedad de Alzheimer: Nuevos Paradigmas. Buenos Aires: Editorial Polemos; 2018.
6. Cairns NJ, Perrin RJ, Franklin EE, Carter D, Vincent B, Xie M, et al. Neuropathologic assessment of participants in two multi-center longitudinal observational studies: the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN). Neuropathology. 2015;35(4):390-400. https://doi.org/10.1111/neup.12205
7. Pievani M, Filippini N, van den Heuvel MP, Cappa SF, Frisoni GB. Brain connectivity in neurodegenerative diseases--from phenotype to protein pathy. Nat Rev Neurol. 2014;10(11):620-33. https://doi.org/10.1038/nrneurol.2014.178
8. Nelson PT, Dickson DW, Trojanowski JQ, Jack CR, Boyle PA, Arfanakis K, et al. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain. 2019;142(6):1503-27. https://doi.org/10.1093/brain/awz099
9. Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006-14. https://doi.org/10.1212/WNL.0b013e31821103e6
10. Takeda S. Progress ion of Alzheimer's disease, tau propagation, and its modifiable risk factors. Neurosci Res. 2019;141:36-42. https://doi.org/10.1016/j.neures.2018.08.005
11. Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007;6(8):734-46. https://doi.org/10.1016/s1474-4422(07)70178-3
12. Jack CR Jr, Albert MS, Knopman DS, McKhann GM, Sperling RA, Carrillo MC, et al. Introduction to the recommendations from the National Institute on Aging - Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):257-62. https://doi.org/10.1016/j.jalz.2011.03.004
13. Jack Jr CR, Bennett DA, Blennow K, Carrillo MC, Feldman HH, Frisoni GB, et al. A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016;87(5):539-47. https://doi.org/10.1212/WNL.0000000000002923
14. Russo MJ, Gustafson S, Vázquez S, Surace E, Guinjoan S, Allegri RF, et al. Creation of the Argentina - Alzheimer Disease Neuroimaging Initiative. Alzheimers Dementia. 2014;10(1 Suppl):S84-7. https://doi.org/10.1016/j.jalz.2013.09.015
15. Carrillo MC, Bain LJ, Frisoni GB, Weiner MW. Worldwide Alzheimer’s disease neuroimaging initiative. Alzheimers Dement. 2012;8(4):337-42. https://doi.org/10.1016/j.jalz.2012.04.007
16. Weiner MW, Aisen PS, Jack Jr CR, Jagust WJ, Trojanowski JQ, Shaw L, et al. The Alzheimer’s Disease Neuroimaging Initiative: progress report and future plans. Alzheimers Dement. 2010;6(3):202-11. https://doi.org/10.1016/j.jalz.2010.03.007
17. Surace E, Cohen G, Chrem Méndez P, Martin ME, Smyth E, Russo G, et al. Latin American Experience with Alzheimer’s disease. Cerebrospinal Fluid Biomarkers. J Am Geriatr Soc. 2013;61(7):1229-31. https://doi.org/10.1111/jgs.12352
18. Harris P, Fernández Suarez M, Surace EI, Chrem Méndez P, Martín ME, Clarens MF, et al. Cognitive reserve and Aβ1-42 in mild cognitive impairment (Argentina - Alzheimer’s Disease Neuroimaging Initiative). Neuropsychiatr Dis Treat. 2015;11:2599-604. https://doi.org/ 10.2147/NDT.S84292
19. Chrem P, Cohen G, Russo MJ, Fernandez M, Nahas F, Russo G, et al. Concordance between 11C-PIB-PET and clinical diagnosis in a memory clinic. Am J Alzheimers Dis Other Demen. 2015;30(6):599-606. https://doi.org/10.1177/1533317515576387
20. Russo MJ, Cohen G, Chrem Mendez P, Campos J, Nahas FE, Surace EI, et al. Predicting episodic memory performance using different biomarkers: results from Argentina-Alzheimer's Disease Neuroimaging Initiative. Neuropsychiatr Dis Treat. 2016;12:2199-206. https://doi.org/10.2147/ndt.s107051
21. Russo MJ, Campos J, Vázquez S, Sevlever G, Allegri RF. Alzheimer's disease neuroimaging initiative. Adding recognition discriminability index to the delayed recall is useful to predict conversion from mild cognitive impairment to Alzheimer's disease in the Alzheimer's disease neuroimaging initiative. Front Aging Neurosci. 2017;9:46. https://doi.org/10.3389/fnagi.2017.00046
22. Russo MJ, Cohen G, Campos J, Martin ME, Clarens MF, Sabe L, et al. Usefulness of discriminability and response bias indices for the evaluation of recognition memory in mild cognitive impairment and Alzheimer disease. Dement Geriatr Cogn Disord. 2017;43(1-2):1-14. https://doi.org/10.1159/000452255
23. Méndez PC, Calandri I, Nahas F, Russo MJ, Demey I, Martín Meet, et al. Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI): neuropsychological evolution profile after one-year follow up. Arq Neuropsiquiatr. 2018;76(4):231-40. https://doi.org/10.1590/0004-282x20180025
24. Russo MJ, Cohen G, Méndez PC, Campos J, Martín ME, Clarens MF, et al. Utility of the Spanish version of the Everyday Cognition scale in the diagnosis of mild cognitive impairment and mild dementia in an older cohort from the Argentina-ADNI. Aging Clin Exp Res. 2018;30(10):1167-76. https://doi.org/10.1007/s40520-018-0899-8
25. Jack Jr CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535-62. https://doi.org/10.1016/j.jalz.2018.02.018
26. Allegri RF, Chrem Mendez P, Calandri I, Cohen G, Martin ME, Russo MJ, et al. Prognostic value of ATN Alzheimer biomarkers: 60-month follow-up results from the Argentine-Alzheimer’s Disease Neuroimaging Initiative. Alzheimers Dementia (Amst). 2020;12(1):e12026. https://doi.org/10.1002/dad2.12026
27. Niikado M, Méndez PC, Itzcovich T, Barbieri-Kennedy M, Calandri I, Martinetto H, et al. Evaluation of cerebrospinal fluid neurofilament light chain as a routine biomarker in a memory clinic. J Gerontol A Biol Sci Med Sci. 2019;74(4):442-5. https://doi.org/10.1093/gerona/gly179
28. Riudavets MA, Bartoloni L, Troncoso JC, Pletnikova O, St George-Hyslop P, Schultz M et al. Familial dementia with frontotemporal features associated with M146V presenilin-1 mutation. Brain Pathol. 2013;23(5):595-600. https://doi.org/10.1111/bpa.12051
29. Itzcovich T, Méndez PC, Vázquez S, Barbieri-Kennedy M, Niikado M, Martinetto H, et al. A novel mutation in PSEN1 (p.T119I) in an Argentine family with early- and late-onset Alzheimer's disease. Neurobiol Aging. 2020;85:155.e9-155.e12. https://doi.org/10.1016/j.neurobiolaging.2019.05.001
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spelling Allegri, Ricardo Franciscovirtual::802-12021-03-12T15:55:18Z2021-03-12T15:55:18Z2020-09-1819805764https://hdl.handle.net/11323/7992https://doi.org/10.1590/1980-57642020dn14-030005Corporación Universidad de la CostaREDICUC - Repositorio CUChttps://repositorio.cuc.edu.co/Neurodegenerative dementias have been described based on their phenotype, in relation to selective degeneration occurring in a particular neuroanatomical system. More recently however, the term proteinopathy has been introduced to describe diseases in which one or more altered proteins can be detected. Neurodegenerative diseases can be produced by more than one abnormal protein and each proteinopathy can determine different clinical phenotypes. Specific biomarkers have now been linked to certain molecular pathologies in live patients. In 2016, a new biomarker-based classification, currently only approved for research in Alzheimer’s disease, was introduced. It is based on the evaluation three biomarkers: amyloid (A) detected on amyloid-PET or amyloid- beta 42 assay in CSF; tau (T) measured in CSF as phosphorylated tau or on tau PET imaging; and neuronal injury/neurodegeneration (N), detected by total T-tau in CSF, FDG PET hypometabolism and on MRI brain scan. Results of clinical research using the ATN biomarkers at FLENI, a Neurological Institute in Buenos Aires, Argentina have, since 2011, contributed to ongoing efforts to move away from the concept of neurodegenerative dementias and more towards one of cognitive proteinopathies. Today, clinical diagnosis in dementia can only tell us “where” abnormal tissue is found but not “what” molecular mechanisms are involvedAllegri, Ricardo Francisco-will be generated-orcid-0000-0001-7166-1234-600application/pdfengCorporación Universidad de la CostaCC0 1.0 Universalhttp://creativecommons.org/publicdomain/zero/1.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Dementia e Neuropsychologiahttps://www.scielo.br/scielo.php?pid=S1980-57642020000300237&script=sci_arttextAlzheimer diseaseProteinsFrontotemporal dementiaBiomarkersDementiaMoving from neurodegenerative dementias, to cognitive proteinopathies, replacing “where” by “what”Artículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/acceptedVersion1. Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012;367(9):795-804. 10.1056/NEJMoa12027532. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984;34(7):939-44. https://doi.org/10.1212/wnl.34.7.9393. Mendez PC, Surace E, Bérgamo Y, Calandri I, Vázquez S, Sevlever G, et al. Biomarkers for Alzheimer's disease. Where we stand and where we are headed. Medicina (B Aires). 2019;79(Spec 6/1):546-51.4. Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol. 2014;13(6):614-29. https://doi.org/10.1016/s1474-4422(14)70090-05. Allegri RF, Vazquez S, Sevlever G. Enfermedad de Alzheimer: Nuevos Paradigmas. Buenos Aires: Editorial Polemos; 2018.6. Cairns NJ, Perrin RJ, Franklin EE, Carter D, Vincent B, Xie M, et al. Neuropathologic assessment of participants in two multi-center longitudinal observational studies: the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN). Neuropathology. 2015;35(4):390-400. https://doi.org/10.1111/neup.122057. Pievani M, Filippini N, van den Heuvel MP, Cappa SF, Frisoni GB. Brain connectivity in neurodegenerative diseases--from phenotype to protein pathy. Nat Rev Neurol. 2014;10(11):620-33. https://doi.org/10.1038/nrneurol.2014.1788. Nelson PT, Dickson DW, Trojanowski JQ, Jack CR, Boyle PA, Arfanakis K, et al. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain. 2019;142(6):1503-27. https://doi.org/10.1093/brain/awz0999. Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006-14. https://doi.org/10.1212/WNL.0b013e31821103e610. Takeda S. Progress ion of Alzheimer's disease, tau propagation, and its modifiable risk factors. Neurosci Res. 2019;141:36-42. https://doi.org/10.1016/j.neures.2018.08.00511. Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007;6(8):734-46. https://doi.org/10.1016/s1474-4422(07)70178-312. Jack CR Jr, Albert MS, Knopman DS, McKhann GM, Sperling RA, Carrillo MC, et al. Introduction to the recommendations from the National Institute on Aging - Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):257-62. https://doi.org/10.1016/j.jalz.2011.03.00413. Jack Jr CR, Bennett DA, Blennow K, Carrillo MC, Feldman HH, Frisoni GB, et al. A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016;87(5):539-47. https://doi.org/10.1212/WNL.000000000000292314. Russo MJ, Gustafson S, Vázquez S, Surace E, Guinjoan S, Allegri RF, et al. Creation of the Argentina - Alzheimer Disease Neuroimaging Initiative. Alzheimers Dementia. 2014;10(1 Suppl):S84-7. https://doi.org/10.1016/j.jalz.2013.09.01515. Carrillo MC, Bain LJ, Frisoni GB, Weiner MW. Worldwide Alzheimer’s disease neuroimaging initiative. Alzheimers Dement. 2012;8(4):337-42. https://doi.org/10.1016/j.jalz.2012.04.00716. Weiner MW, Aisen PS, Jack Jr CR, Jagust WJ, Trojanowski JQ, Shaw L, et al. The Alzheimer’s Disease Neuroimaging Initiative: progress report and future plans. Alzheimers Dement. 2010;6(3):202-11. https://doi.org/10.1016/j.jalz.2010.03.00717. Surace E, Cohen G, Chrem Méndez P, Martin ME, Smyth E, Russo G, et al. Latin American Experience with Alzheimer’s disease. Cerebrospinal Fluid Biomarkers. J Am Geriatr Soc. 2013;61(7):1229-31. https://doi.org/10.1111/jgs.1235218. Harris P, Fernández Suarez M, Surace EI, Chrem Méndez P, Martín ME, Clarens MF, et al. Cognitive reserve and Aβ1-42 in mild cognitive impairment (Argentina - Alzheimer’s Disease Neuroimaging Initiative). Neuropsychiatr Dis Treat. 2015;11:2599-604. https://doi.org/ 10.2147/NDT.S8429219. Chrem P, Cohen G, Russo MJ, Fernandez M, Nahas F, Russo G, et al. Concordance between 11C-PIB-PET and clinical diagnosis in a memory clinic. Am J Alzheimers Dis Other Demen. 2015;30(6):599-606. https://doi.org/10.1177/153331751557638720. Russo MJ, Cohen G, Chrem Mendez P, Campos J, Nahas FE, Surace EI, et al. Predicting episodic memory performance using different biomarkers: results from Argentina-Alzheimer's Disease Neuroimaging Initiative. Neuropsychiatr Dis Treat. 2016;12:2199-206. https://doi.org/10.2147/ndt.s10705121. Russo MJ, Campos J, Vázquez S, Sevlever G, Allegri RF. Alzheimer's disease neuroimaging initiative. Adding recognition discriminability index to the delayed recall is useful to predict conversion from mild cognitive impairment to Alzheimer's disease in the Alzheimer's disease neuroimaging initiative. Front Aging Neurosci. 2017;9:46. https://doi.org/10.3389/fnagi.2017.0004622. Russo MJ, Cohen G, Campos J, Martin ME, Clarens MF, Sabe L, et al. Usefulness of discriminability and response bias indices for the evaluation of recognition memory in mild cognitive impairment and Alzheimer disease. Dement Geriatr Cogn Disord. 2017;43(1-2):1-14. https://doi.org/10.1159/00045225523. Méndez PC, Calandri I, Nahas F, Russo MJ, Demey I, Martín Meet, et al. Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI): neuropsychological evolution profile after one-year follow up. Arq Neuropsiquiatr. 2018;76(4):231-40. https://doi.org/10.1590/0004-282x2018002524. Russo MJ, Cohen G, Méndez PC, Campos J, Martín ME, Clarens MF, et al. Utility of the Spanish version of the Everyday Cognition scale in the diagnosis of mild cognitive impairment and mild dementia in an older cohort from the Argentina-ADNI. Aging Clin Exp Res. 2018;30(10):1167-76. https://doi.org/10.1007/s40520-018-0899-825. Jack Jr CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535-62. https://doi.org/10.1016/j.jalz.2018.02.01826. Allegri RF, Chrem Mendez P, Calandri I, Cohen G, Martin ME, Russo MJ, et al. Prognostic value of ATN Alzheimer biomarkers: 60-month follow-up results from the Argentine-Alzheimer’s Disease Neuroimaging Initiative. Alzheimers Dementia (Amst). 2020;12(1):e12026. https://doi.org/10.1002/dad2.1202627. Niikado M, Méndez PC, Itzcovich T, Barbieri-Kennedy M, Calandri I, Martinetto H, et al. Evaluation of cerebrospinal fluid neurofilament light chain as a routine biomarker in a memory clinic. J Gerontol A Biol Sci Med Sci. 2019;74(4):442-5. https://doi.org/10.1093/gerona/gly17928. Riudavets MA, Bartoloni L, Troncoso JC, Pletnikova O, St George-Hyslop P, Schultz M et al. Familial dementia with frontotemporal features associated with M146V presenilin-1 mutation. Brain Pathol. 2013;23(5):595-600. https://doi.org/10.1111/bpa.1205129. Itzcovich T, Méndez PC, Vázquez S, Barbieri-Kennedy M, Niikado M, Martinetto H, et al. A novel mutation in PSEN1 (p.T119I) in an Argentine family with early- and late-onset Alzheimer's disease. 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