New Biomarker for Alzheimer's Disease Diagnostic

NCT01315639 | Completed

• 1 other identifier: P081205
• Study Type: interventional
• Target: 1,067
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to examine the relationship between plasma putative biomarkers for Alzheimer's disease (i.e. Ab40 amyloid and total Ab42 amyloid, free, bound, free/bound, truncated, sAPPα) and :

• the risk of conversion of individuals with Mild Cognitive Impairment (MCI) into Alzheimer's disease (AD),
• the Alzheimer's disease progression rate.

Conditions

Alzheimer's Disease; Mild Cognitive Impairment

Keywords

Dementia; Cognitive impairment; Memory impairment; Mild Cognitive Impairment; Cerebrospinal fluid; Plasma; Biomarker; Longitudinal; Abeta peptide amyloid, saPP alpha; Oculomotor impairment

Outcome Measures

Primary Outcomes (2)

• Mean concentration of plasma AB peptides

  * MCI "converted" (MCI-AD) * and stable MCI (MCI-MCI) groups

  at t0 and 24 months

• plasma levels of Tau protein

  Ancillary study :comparison of plasma levels of Tau protein at baseline between MCI converters and MCI non-converters and between rapidly and non-rapidly progressing AD.

  t0

Secondary Outcomes (12)

• Mean concentration of biomarker

  t0 and 24 months

• MRI

  T0 + M24 or conversion

• Transcriptomics biomarkers

  T0 and 24 months or conversions

• Bace peptide

  t0

• TACE/ADAM17

  to

Study Arms (1)

biomarkers, MRI and CSF

OTHER

Longitudinal multicenter study including 1300 subjects with amnestic impairment (MCI, n=650 and AD, n=650) derived from the main French national Memory Resources and Research Centers. Participants will undergo at baseline and every 6 months a neurological examination, a neuropsychological assessment (and an oculomotor examination for those included from Broca Hospital). Alzheimer disease biomarkers' measurements will be performed at inclusion and at the end of the study (or the conversion).

Biological: biomarkers, MRI and CSF

Interventions

biomarkers, MRI and CSF BIOLOGICAL

MRI at Day 0 and month 24 (or conversion) Biomarkers at Day 0 et month 24 (or conversion) CSF at D0

biomarkers, MRI and CSF

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• MCI group :
• ≥ 70 years
• MCI diagnosis : New criteria (Petersen, PORTET\*)
• cognitive complaint from the patient, family, or both,
• report by the subject or reporter of a decline in cognitive or functional performance, relative to previous abilities,
• cognitive disorders evidenced by clinical evaluation: impairment in memory or another cognitive domain,
• cognitive impairment without any repercussion on daily life, even if the subject reports difficulties concerning complex daily activities,
• no dementia
• Having signed an informed consent form
• Fluent in French
• AD group :
• ≥ 45 years
• AD diagnosis (DSM IV-TR et NINCDS-ADRDA)
• Mild to moderate (MMSE \> 15)
• Having signed an informed consent form

You may not qualify if:

• Normal cognitive function
• Major depression (according to the DSMIV-TR or MINI or Geriatric depression Scale\> 20/30)
• Genetic form of AD (genetic mutation known)
• All other diseases that could interfere with cognitive assessment (Epilepsy, Parkinson's disease, schizophrenia, other dementia)
• Major sensory deficits that could interfere with cognitive assessment (visual and auditory)
• Diseases involving the short-term survival (advanced cancer, unstable heart disease, severe hepatic/respiratory/renal failure)
• Contraindication for MRI, for lumbar puncture (i.e. anticoagulant agents)
• Use of any experimental agent for the duration of the study
• Participation to other biomedical research that could interfere with principal objective of the study
• Less than 4 years of education
• Illiteracy, is unable to count or to read
• Pregnant women
• Non health insurance affiliation
• Private subjects of freedom by legal or administrative decision
• Contraindication for MRI examination:

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

APHP, Hôpital Broca

Paris, 75013, France

Location

Related Publications (16)

• Hanon O, Vidal JS, Lehmann S, Bombois S, Allinquant B, Treluyer JM, Gele P, Delmaire C, Blanc F, Mangin JF, Buee L, Touchon J, Hugon J, Vellas B, Galbrun E, Benetos A, Berrut G, Paillaud E, Wallon D, Castelnovo G, Volpe-Gillot L, Paccalin M, Robert PH, Godefroy O, Dantoine T, Camus V, Belmin J, Vandel P, Novella JL, Duron E, Rigaud AS, Schraen-Maschke S, Gabelle A; BALTAZAR study group. Plasma amyloid levels within the Alzheimer's process and correlations with central biomarkers. Alzheimers Dement. 2018 Jul;14(7):858-868. doi: 10.1016/j.jalz.2018.01.004. Epub 2018 Feb 17.

  PMID: 29458036 BACKGROUND

• Hanon O, Vidal JS, Lehmann S, Bombois S, Allinquant B, Baret-Rose C, Treluyer JM, Abdoul H, Gele P, Delmaire C, Blanc F, Mangin JF, Buee L, Touchon J, Hugon J, Vellas B, Galbrun E, Benetos A, Berrut G, Paillaud E, Wallon D, Castelnovo G, Volpe-Gillot L, Paccalin M, Robert P, Godefroy O, Camus V, Belmin J, Vandel P, Novella JL, Duron E, Rigaud AS, Schraen-Maschke S, Gabelle A; BALTAZAR study group. Plasma amyloid beta predicts conversion to dementia in subjects with mild cognitive impairment: The BALTAZAR study. Alzheimers Dement. 2022 Dec;18(12):2537-2550. doi: 10.1002/alz.12613. Epub 2022 Feb 20.

  PMID: 35187794 BACKGROUND

• Duron E, Vidal JS, Grousselle D, Gabelle A, Lehmann S, Pasquier F, Bombois S, Buee L, Allinquant B, Schraen-Maschke S, Baret C, Rigaud AS, Hanon O, Epelbaum J. Corrigendum: Somatostatin and Neuropeptide Y in Cerebrospinal Fluid: Correlations With Amyloid Peptides Ass1-42, and Tau Proteins in Elderly Patients With Mild Cognitive Impairment. Front Aging Neurosci. 2019 Feb 19;11:11. doi: 10.3389/fnagi.2019.00011. eCollection 2019.

  PMID: 30837862 BACKGROUND

• Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC, Boland A, Vronskaya M, van der Lee SJ, Amlie-Wolf A, Bellenguez C, Frizatti A, Chouraki V, Martin ER, Sleegers K, Badarinarayan N, Jakobsdottir J, Hamilton-Nelson KL, Moreno-Grau S, Olaso R, Raybould R, Chen Y, Kuzma AB, Hiltunen M, Morgan T, Ahmad S, Vardarajan BN, Epelbaum J, Hoffmann P, Boada M, Beecham GW, Garnier JG, Harold D, Fitzpatrick AL, Valladares O, Moutet ML, Gerrish A, Smith AV, Qu L, Bacq D, Denning N, Jian X, Zhao Y, Del Zompo M, Fox NC, Choi SH, Mateo I, Hughes JT, Adams HH, Malamon J, Sanchez-Garcia F, Patel Y, Brody JA, Dombroski BA, Naranjo MCD, Daniilidou M, Eiriksdottir G, Mukherjee S, Wallon D, Uphill J, Aspelund T, Cantwell LB, Garzia F, Galimberti D, Hofer E, Butkiewicz M, Fin B, Scarpini E, Sarnowski C, Bush WS, Meslage S, Kornhuber J, White CC, Song Y, Barber RC, Engelborghs S, Sordon S, Voijnovic D, Adams PM, Vandenberghe R, Mayhaus M, Cupples LA, Albert MS, De Deyn PP, Gu W, Himali JJ, Beekly 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S, Quinn JF, Sacchinelli E, Raj A, Spalletta G, Raskind M, Caltagirone C, Bossu P, Orfei MD, Reisberg B, Clarke R, Reitz C, Smith AD, Ringman JM, Warden D, Roberson ED, Wilcock G, Rogaeva E, Bruni AC, Rosen HJ, Gallo M, Rosenberg RN, Ben-Shlomo Y, Sager MA, Mecocci P, Saykin AJ, Pastor P, Cuccaro ML, Vance JM, Schneider JA, Schneider LS, Slifer S, Seeley WW, Smith AG, Sonnen JA, Spina S, Stern RA, Swerdlow RH, Tang M, Tanzi RE, Trojanowski JQ, Troncoso JC, Van Deerlin VM, Van Eldik LJ, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Wilhelmsen KC, Williamson J, Wingo TS, Woltjer RL, Wright CB, Yu CE, Yu L, Saba Y, Pilotto A, Bullido MJ, Peters O, Crane PK, Bennett D, Bosco P, Coto E, Boccardi V, De Jager PL, Lleo A, Warner N, Lopez OL, Ingelsson M, Deloukas P, Cruchaga C, Graff C, Gwilliam R, Fornage M, Goate AM, Sanchez-Juan P, Kehoe PG, Amin N, Ertekin-Taner N, Berr C, Debette S, Love S, Launer LJ, Younkin SG, Dartigues JF, Corcoran C, Ikram MA, Dickson DW, Nicolas G, Campion D, Tschanz J, Schmidt H, Hakonarson H, Clarimon J, Munger R, Schmidt R, Farrer LA, Van Broeckhoven C, C O'Donovan M, DeStefano AL, Jones L, Haines JL, Deleuze JF, Owen MJ, Gudnason V, Mayeux R, Escott-Price V, Psaty BM, Ramirez A, Wang LS, Ruiz A, van Duijn CM, Holmans PA, Seshadri S, Williams J, Amouyel P, Schellenberg GD, Lambert JC, Pericak-Vance MA; Alzheimer Disease Genetics Consortium (ADGC),; European Alzheimer's Disease Initiative (EADI),; Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE),; Genetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer's Disease Consortium (GERAD/PERADES),. Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing. Nat Genet. 2019 Mar;51(3):414-430. doi: 10.1038/s41588-019-0358-2. Epub 2019 Feb 28.

  PMID: 30820047 BACKGROUND

• de Rojas I, Moreno-Grau S, Tesi N, Grenier-Boley B, Andrade V, Jansen IE, Pedersen NL, Stringa N, Zettergren A, Hernandez I, Montrreal L, Antunez C, Antonell A, Tankard RM, Bis JC, Sims R, Bellenguez C, Quintela I, Gonzalez-Perez A, Calero M, Franco-Macias E, Macias J, Blesa R, Cervera-Carles L, Menendez-Gonzalez M, Frank-Garcia A, Royo JL, Moreno F, Huerto Vilas R, Baquero M, Diez-Fairen M, Lage C, Garcia-Madrona S, Garcia-Gonzalez P, Alarcon-Martin E, Valero S, Sotolongo-Grau O, Ullgren A, Naj AC, Lemstra AW, Benaque A, Perez-Cordon A, Benussi A, Rabano A, Padovani A, Squassina A, de Mendonca A, Arias Pastor A, Kok AAL, Meggy A, Pastor AB, Espinosa A, Corma-Gomez A, Martin Montes A, Sanabria A, DeStefano AL, Schneider A, Haapasalo A, Kinhult Stahlbom A, Tybjaerg-Hansen A, Hartmann AM, Spottke A, Corbaton-Anchuelo A, Rongve A, Borroni B, Arosio B, Nacmias B, Nordestgaard BG, Kunkle BW, Charbonnier C, Abdelnour C, Masullo C, Martinez Rodriguez C, Munoz-Fernandez C, Dufouil C, Graff C, Ferreira CB, Chillotti C, Reynolds CA, Fenoglio C, Van Broeckhoven C, Clark C, Pisanu C, Satizabal CL, Holmes C, Buiza-Rueda D, Aarsland D, Rujescu D, Alcolea D, Galimberti D, Wallon D, Seripa D, Grunblatt E, Dardiotis E, Duzel E, Scarpini E, Conti E, Rubino E, Gelpi E, Rodriguez-Rodriguez E, Duron E, Boerwinkle E, Ferri E, Tagliavini F, Kucukali F, Pasquier F, Sanchez-Garcia F, Mangialasche F, Jessen F, Nicolas G, Selbaek G, Ortega G, Chene G, Hadjigeorgiou G, Rossi G, Spalletta G, Giaccone G, Grande G, Binetti G, Papenberg G, Hampel H, Bailly H, Zetterberg H, Soininen H, Karlsson IK, Alvarez I, Appollonio I, Giegling I, Skoog I, Saltvedt I, Rainero I, Rosas Allende I, Hort J, Diehl-Schmid J, Van Dongen J, Vidal JS, Lehtisalo J, Wiltfang J, Thomassen JQ, Kornhuber J, Haines JL, Vogelgsang J, Pineda JA, Fortea J, Popp J, Deckert J, Buerger K, Morgan K, Fliessbach K, Sleegers K, Molina-Porcel L, Kilander L, Weinhold L, Farrer LA, Wang LS, Kleineidam L, Farotti L, Parnetti L, Tremolizzo L, Hausner L, Benussi L, Froelich L, Ikram MA, Deniz-Naranjo MC, Tsolaki M, Rosende-Roca M, Lowenmark M, Hulsman M, Spallazzi M, Pericak-Vance MA, Esiri M, Bernal Sanchez-Arjona M, Dalmasso MC, Martinez-Larrad MT, Arcaro M, Nothen MM, Fernandez-Fuertes M, Dichgans M, Ingelsson M, Herrmann MJ, Scherer M, Vyhnalek M, Kosmidis MH, Yannakoulia M, Schmid M, Ewers M, Heneka MT, Wagner M, Scamosci M, Kivipelto M, Hiltunen M, Zulaica M, Alegret M, Fornage M, Roberto N, van Schoor NM, Seidu NM, Banaj N, Armstrong NJ, Scarmeas N, Scherbaum N, Goldhardt O, Hanon O, Peters O, Skrobot OA, Quenez O, Lerch O, Bossu P, Caffarra P, Dionigi Rossi P, Sakka P, Mecocci P, Hoffmann P, Holmans PA, Fischer P, Riederer P, Yang Q, Marshall R, Kalaria RN, Mayeux R, Vandenberghe R, Cecchetti R, Ghidoni R, Frikke-Schmidt R, Sorbi S, Hagg S, Engelborghs S, Helisalmi S, Botne Sando S, Kern S, Archetti S, Boschi S, Fostinelli S, Gil S, Mendoza S, Mead S, Ciccone S, Djurovic S, Heilmann-Heimbach S, Riedel-Heller S, Kuulasmaa T, Del Ser T, Lebouvier T, Polak T, Ngandu T, Grimmer T, Bessi V, Escott-Price V, Giedraitis V, Deramecourt V, Maier W, Jian X, Pijnenburg YAL; EADB contributors; GR@ACE study group; DEGESCO consortium; IGAP (ADGC, CHARGE, EADI, GERAD); PGC-ALZ consortia; Kehoe PG, Garcia-Ribas G, Sanchez-Juan P, Pastor P, Perez-Tur J, Pinol-Ripoll G, Lopez de Munain A, Garcia-Alberca JM, Bullido MJ, Alvarez V, Lleo A, Real LM, Mir P, Medina M, Scheltens P, Holstege H, Marquie M, Saez ME, Carracedo A, Amouyel P, Schellenberg GD, Williams J, Seshadri S, van Duijn CM, Mather KA, Sanchez-Valle R, Serrano-Rios M, Orellana A, Tarraga L, Blennow K, Huisman M, Andreassen OA, Posthuma D, Clarimon J, Boada M, van der Flier WM, Ramirez A, Lambert JC, van der Lee SJ, Ruiz A. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores. Nat Commun. 2021 Jun 7;12(1):3417. doi: 10.1038/s41467-021-22491-8.

  PMID: 34099642 BACKGROUND

• Jansen IE, van der Lee SJ, Gomez-Fonseca D, de Rojas I, Dalmasso MC, Grenier-Boley B, Zettergren A, Mishra A, Ali M, Andrade V, Bellenguez C, Kleineidam L, Kucukali F, Sung YJ, Tesi N, Vromen EM, Wightman DP, Alcolea D, Alegret M, Alvarez I, Amouyel P, Athanasiu L, Bahrami S, Bailly H, Belbin O, Bergh S, Bertram L, Biessels GJ, Blennow K, Blesa R, Boada M, Boland A, Buerger K, Carracedo A, Cervera-Carles L, Chene G, Claassen JAHR, Debette S, Deleuze JF, de Deyn PP, Diehl-Schmid J, Djurovic S, Dols-Icardo O, Dufouil C, Duron E, Duzel E; EADB consortium; Fladby T, Fortea J, Frolich L, Garcia-Gonzalez P, Garcia-Martinez M, Giegling I, Goldhardt O, Gobom J, Grimmer T, Haapasalo A, Hampel H, Hanon O, Hausner L, Heilmann-Heimbach S, Helisalmi S, Heneka MT, Hernandez I, Herukka SK, Holstege H, Jarholm J, Kern S, Knapskog AB, Koivisto AM, Kornhuber J, Kuulasmaa T, Lage C, Laske C, Leinonen V, Lewczuk P, Lleo A, de Munain AL, Lopez-Garcia S, Maier W, Marquie M, Mol MO, Montrreal L, Moreno F, Moreno-Grau S, Nicolas G, Nothen MM, Orellana A, Palhaugen L, Papma JM, Pasquier F, Perneczky R, Peters O, Pijnenburg YAL, Popp J, Posthuma D, Pozueta A, Priller J, Puerta R, Quintela I, Ramakers I, Rodriguez-Rodriguez E, Rujescu D, Saltvedt I, Sanchez-Juan P, Scheltens P, Scherbaum N, Schmid M, Schneider A, Selbaek G, Selnes P, Shadrin A, Skoog I, Soininen H, Tarraga L, Teipel S; GR@ACE study group; Tijms B, Tsolaki M, Van Broeckhoven C, Van Dongen J, van Swieten JC, Vandenberghe R, Vidal JS, Visser PJ, Vogelgsang J, Waern M, Wagner M, Wiltfang J, Wittens MMJ, Zetterberg H, Zulaica M, van Duijn CM, Bjerke M, Engelborghs S, Jessen F, Teunissen CE, Pastor P, Hiltunen M, Ingelsson M, Andreassen OA, Clarimon J, Sleegers K, Ruiz A, Ramirez A, Cruchaga C, Lambert JC, van der Flier W. Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers. Acta Neuropathol. 2022 Nov;144(5):821-842. doi: 10.1007/s00401-022-02454-z. Epub 2022 Sep 6.

  PMID: 36066633 BACKGROUND

• Le Guen Y, Belloy ME, Grenier-Boley B, de Rojas I, Castillo-Morales A, Jansen I, Nicolas A, Bellenguez C, Dalmasso C, Kucukali F, Eger SJ, Rasmussen KL, Thomassen JQ, Deleuze JF, He Z, Napolioni V, Amouyel P, Jessen F, Kehoe PG, van Duijn C, Tsolaki M, Sanchez-Juan P, Sleegers K, Ingelsson M, Rossi G, Hiltunen M, Sims R, van der Flier WM, Ramirez A, Andreassen OA, Frikke-Schmidt R, Williams J, Ruiz A, Lambert JC, Greicius MD; Members of the EADB, GR@ACE, DEGESCO, DemGene, GERAD, and EADI Groups; Arosio B, Benussi L, Boland A, Borroni B, Caffarra P, Daian D, Daniele A, Debette S, Dufouil C, Duzel E, Galimberti D, Giedraitis V, Grimmer T, Graff C, Grunblatt E, Hanon O, Hausner L, Heilmann-Heimbach S, Holstege H, Hort J, Jurgen D, Kuulasmaa T, van der Lugt A, Masullo C, Mecocci P, Mehrabian S, de Mendonca A, Moebus S, Nacmias B, Nicolas G, Olaso R, Papenberg G, Parnetti L, Pasquier F, Peters O, Pijnenburg YAL, Popp J, Rainero I, Ramakers I, Riedel-Heller S, Scarmeas N, Scheltens P, Scherbaum N, Schneider A, Seripa D, Soininen H, Solfrizzi V, Spalletta G, Squassina A, van Swieten J, Tegos TJ, Tremolizzo L, Verhey F, Vyhnalek M, Wiltfang J, Boada M, Garcia-Gonzalez P, Puerta R, Real LM, Alvarez V, Bullido MJ, Clarimon J, Garcia-Alberca JM, Mir P, Moreno F, Pastor P, Pinol-Ripoll G, Molina-Porcel L, Perez-Tur J, Rodriguez-Rodriguez E, Royo JL, Sanchez-Valle R, Dichgans M, Rujescu D. Association of Rare APOE Missense Variants V236E and R251G With Risk of Alzheimer Disease. JAMA Neurol. 2022 Jul 1;79(7):652-663. doi: 10.1001/jamaneurol.2022.1166.

  PMID: 35639372 BACKGROUND

• Bellenguez C, Kucukali F, Jansen IE, Kleineidam L, Moreno-Grau S, Amin N, Naj AC, Campos-Martin R, Grenier-Boley B, Andrade V, Holmans PA, Boland A, Damotte V, van der Lee SJ, Costa MR, Kuulasmaa T, Yang Q, de Rojas I, Bis JC, Yaqub A, Prokic I, Chapuis J, Ahmad S, Giedraitis V, Aarsland D, Garcia-Gonzalez P, Abdelnour C, Alarcon-Martin E, Alcolea D, Alegret M, Alvarez I, Alvarez V, Armstrong NJ, Tsolaki A, Antunez C, Appollonio I, Arcaro M, Archetti S, Pastor AA, Arosio B, Athanasiu L, Bailly H, Banaj N, Baquero M, Barral S, Beiser A, Pastor AB, Below JE, Benchek P, Benussi L, Berr C, Besse C, Bessi V, Binetti G, Bizarro A, Blesa R, Boada M, Boerwinkle E, Borroni B, Boschi S, Bossu P, Brathen G, Bressler J, Bresner C, Brodaty H, Brookes KJ, Brusco LI, Buiza-Rueda D, Burger K, Burholt V, Bush WS, Calero M, Cantwell LB, Chene G, Chung J, Cuccaro ML, Carracedo A, Cecchetti R, Cervera-Carles L, Charbonnier C, Chen HH, Chillotti C, Ciccone S, Claassen JAHR, Clark C, Conti E, Corma-Gomez A, Costantini E, Custodero C, Daian D, Dalmasso MC, Daniele A, Dardiotis E, Dartigues JF, de Deyn PP, de Paiva Lopes K, de Witte LD, Debette S, Deckert J, Del Ser T, Denning N, DeStefano A, Dichgans M, Diehl-Schmid J, Diez-Fairen M, Rossi PD, Djurovic S, Duron E, Duzel E, Dufouil C, Eiriksdottir G, Engelborghs S, Escott-Price V, Espinosa A, Ewers M, Faber KM, Fabrizio T, Nielsen SF, Fardo DW, Farotti L, Fenoglio C, Fernandez-Fuertes M, Ferrari R, Ferreira CB, Ferri E, Fin B, Fischer P, Fladby T, Fliessbach K, Fongang B, Fornage M, Fortea J, Foroud TM, Fostinelli S, Fox NC, Franco-Macias E, Bullido MJ, Frank-Garcia A, Froelich L, Fulton-Howard B, Galimberti D, Garcia-Alberca JM, Garcia-Gonzalez P, Garcia-Madrona S, Garcia-Ribas G, Ghidoni R, Giegling I, Giorgio G, Goate AM, Goldhardt O, Gomez-Fonseca D, Gonzalez-Perez A, Graff C, Grande G, Green E, Grimmer T, Grunblatt E, Grunin M, Gudnason V, Guetta-Baranes T, Haapasalo A, Hadjigeorgiou G, Haines JL, Hamilton-Nelson KL, Hampel H, Hanon O, Hardy J, Hartmann AM, Hausner L, Harwood J, Heilmann-Heimbach S, Helisalmi S, Heneka MT, Hernandez I, Herrmann MJ, Hoffmann P, Holmes C, Holstege H, Vilas RH, Hulsman M, Humphrey J, Biessels GJ, Jian X, Johansson C, Jun GR, Kastumata Y, Kauwe J, Kehoe PG, Kilander L, Stahlbom AK, Kivipelto M, Koivisto A, Kornhuber J, Kosmidis MH, Kukull WA, Kuksa PP, Kunkle BW, Kuzma AB, Lage C, Laukka EJ, Launer L, Lauria A, Lee CY, Lehtisalo J, Lerch O, Lleo A, Longstreth W Jr, Lopez O, de Munain AL, Love S, Lowemark M, Luckcuck L, Lunetta KL, Ma Y, Macias J, MacLeod CA, Maier W, Mangialasche F, Spallazzi M, Marquie M, Marshall R, Martin ER, Montes AM, Rodriguez CM, Masullo C, Mayeux R, Mead S, Mecocci P, Medina M, Meggy A, Mehrabian S, Mendoza S, Menendez-Gonzalez M, Mir P, Moebus S, Mol M, Molina-Porcel L, Montrreal L, Morelli L, Moreno F, Morgan K, Mosley T, Nothen MM, Muchnik C, Mukherjee S, Nacmias B, Ngandu T, Nicolas G, Nordestgaard BG, Olaso R, Orellana A, Orsini M, Ortega G, Padovani A, Paolo C, Papenberg G, Parnetti L, Pasquier F, Pastor P, Peloso G, Perez-Cordon A, Perez-Tur J, Pericard P, Peters O, Pijnenburg YAL, Pineda JA, Pinol-Ripoll G, Pisanu C, Polak T, Popp J, Posthuma D, Priller J, Puerta R, Quenez O, Quintela I, Thomassen JQ, Rabano A, Rainero I, Rajabli F, Ramakers I, Real LM, Reinders MJT, Reitz C, Reyes-Dumeyer D, Ridge P, Riedel-Heller S, Riederer P, Roberto N, Rodriguez-Rodriguez E, Rongve A, Allende IR, Rosende-Roca M, Royo JL, Rubino E, Rujescu D, Saez ME, Sakka P, Saltvedt I, Sanabria A, Sanchez-Arjona MB, Sanchez-Garcia F, Juan PS, Sanchez-Valle R, Sando SB, Sarnowski C, Satizabal CL, Scamosci M, Scarmeas N, Scarpini E, Scheltens P, Scherbaum N, Scherer M, Schmid M, Schneider A, Schott JM, Selbaek G, Seripa D, Serrano M, Sha J, Shadrin AA, Skrobot O, Slifer S, Snijders GJL, Soininen H, Solfrizzi V, Solomon A, Song Y, Sorbi S, Sotolongo-Grau O, Spalletta G, Spottke A, Squassina A, Stordal E, Tartan JP, Tarraga L, Tesi N, Thalamuthu A, Thomas T, Tosto G, Traykov L, Tremolizzo L, Tybjaerg-Hansen A, Uitterlinden A, Ullgren A, Ulstein I, Valero S, Valladares O, Broeckhoven CV, Vance J, Vardarajan BN, van der Lugt A, Dongen JV, van Rooij J, van Swieten J, Vandenberghe R, Verhey F, Vidal JS, Vogelgsang J, Vyhnalek M, Wagner M, Wallon D, Wang LS, Wang R, Weinhold L, Wiltfang J, Windle G, Woods B, Yannakoulia M, Zare H, Zhao Y, Zhang X, Zhu C, Zulaica M; EADB; GR@ACE; DEGESCO; EADI; GERAD; Demgene; FinnGen; ADGC; CHARGE; Farrer LA, Psaty BM, Ghanbari M, Raj T, Sachdev P, Mather K, Jessen F, Ikram MA, de Mendonca A, Hort J, Tsolaki M, Pericak-Vance MA, Amouyel P, Williams J, Frikke-Schmidt R, Clarimon J, Deleuze JF, Rossi G, Seshadri S, Andreassen OA, Ingelsson M, Hiltunen M, Sleegers K, Schellenberg GD, van Duijn CM, Sims R, van der Flier WM, Ruiz A, Ramirez A, Lambert JC. New insights into the genetic etiology of Alzheimer's disease and related dementias. Nat Genet. 2022 Apr;54(4):412-436. doi: 10.1038/s41588-022-01024-z. Epub 2022 Apr 4.

  PMID: 35379992 BACKGROUND

• Le Guen Y, Luo G, Ambati A, Damotte V, Jansen I, Yu E, Nicolas A, de Rojas I, Peixoto Leal T, Miyashita A, Bellenguez C, Lian MM, Parveen K, Morizono T, Park H, Grenier-Boley B, Naito T, Kucukali F, Talyansky SD, Yogeshwar SM, Sempere V, Satake W, Alvarez V, Arosio B, Belloy ME, Benussi L, Boland A, Borroni B, Bullido MJ, Caffarra P, Clarimon J, Daniele A, Darling D, Debette S, Deleuze JF, Dichgans M, Dufouil C, During E, Duzel E, Galimberti D, Garcia-Ribas G, Garcia-Alberca JM, Garcia-Gonzalez P, Giedraitis V, Goldhardt O, Graff C, Grunblatt E, Hanon O, Hausner L, Heilmann-Heimbach S, Holstege H, Hort J, Jung YJ, Jurgen D, Kern S, Kuulasmaa T, Lee KH, Lin L, Masullo C, Mecocci P, Mehrabian S, de Mendonca A, Boada M, Mir P, Moebus S, Moreno F, Nacmias B, Nicolas G, Niida S, Nordestgaard BG, Papenberg G, Papma J, Parnetti L, Pasquier F, Pastor P, Peters O, Pijnenburg YAL, Pinol-Ripoll G, Popp J, Porcel LM, Puerta R, Perez-Tur J, Rainero I, Ramakers I, Real LM, Riedel-Heller S, Rodriguez-Rodriguez E, Ross OA, Royo LJ, Rujescu D, Scarmeas N, Scheltens P, Scherbaum N, Schneider A, Seripa D, Skoog I, Solfrizzi V, Spalletta G, Squassina A, van Swieten J, Sanchez-Valle R, Tan EK, Tegos T, Teunissen C, Thomassen JQ, Tremolizzo L, Vyhnalek M, Verhey F, Waern M, Wiltfang J, Zhang J; EADB; GR@ACE study group; DEGESCO consortium; DemGene; EADI; GERAD; Asian Parkinson's Disease Genetics consortium; Zetterberg H, Blennow K, He Z, Williams J, Amouyel P, Jessen F, Kehoe PG, Andreassen OA, Van Duin C, Tsolaki M, Sanchez-Juan P, Frikke-Schmidt R, Sleegers K, Toda T, Zettergren A, Ingelsson M, Okada Y, Rossi G, Hiltunen M, Gim J, Ozaki K, Sims R, Foo JN, van der Flier W, Ikeuchi T, Ramirez A, Mata I, Ruiz A, Gan-Or Z, Lambert JC, Greicius MD, Mignot E. Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes. Proc Natl Acad Sci U S A. 2023 Sep 5;120(36):e2302720120. doi: 10.1073/pnas.2302720120. Epub 2023 Aug 29.

  PMID: 37643212 BACKGROUND

• de Rojas I, Moreno-Grau S, Tesi N, Grenier-Boley B, Andrade V, Jansen IE, Pedersen NL, Stringa N, Zettergren A, Hernandez I, Montrreal L, Antunez C, Antonell A, Tankard RM, Bis JC, Sims R, Bellenguez C, Quintela I, Gonzalez-Perez A, Calero M, Franco-Macias E, Macias J, Blesa R, Cervera-Carles L, Menendez-Gonzalez M, Frank-Garcia A, Royo JL, Moreno F, Huerto Vilas R, Baquero M, Diez-Fairen M, Lage C, Garcia-Madrona S, Garcia-Gonzalez P, Alarcon-Martin E, Valero S, Sotolongo-Grau O, Ullgren A, Naj AC, Lemstra AW, Benaque A, Perez-Cordon A, Benussi A, Rabano A, Padovani A, Squassina A, de Mendonca A, Arias Pastor A, Kok AAL, Meggy A, Pastor AB, Espinosa A, Corma-Gomez A, Martin Montes A, Sanabria A, DeStefano AL, Schneider A, Haapasalo A, Kinhult Stahlbom A, Tybjaerg-Hansen A, Hartmann AM, Spottke A, Corbaton-Anchuelo A, Rongve A, Borroni B, Arosio B, Nacmias B, Nordestgaard BG, Kunkle BW, Charbonnier C, Abdelnour C, Masullo C, Martinez Rodriguez C, Munoz-Fernandez C, Dufouil C, Graff C, Ferreira CB, Chillotti C, Reynolds CA, Fenoglio C, Van Broeckhoven C, Clark C, Pisanu C, Satizabal CL, Holmes C, Buiza-Rueda D, Aarsland D, Rujescu D, Alcolea D, Galimberti D, Wallon D, Seripa D, Grunblatt E, Dardiotis E, Duzel E, Scarpini E, Conti E, Rubino E, Gelpi E, Rodriguez-Rodriguez E, Duron E, Boerwinkle E, Ferri E, Tagliavini F, Kucukali F, Pasquier F, Sanchez-Garcia F, Mangialasche F, Jessen F, Nicolas G, Selbaek G, Ortega G, Chene G, Hadjigeorgiou G, Rossi G, Spalletta G, Giaccone G, Grande G, Binetti G, Papenberg G, Hampel H, Bailly H, Zetterberg H, Soininen H, Karlsson IK, Alvarez I, Appollonio I, Giegling I, Skoog I, Saltvedt I, Rainero I, Rosas Allende I, Hort J, Diehl-Schmid J, Van Dongen J, Vidal JS, Lehtisalo J, Wiltfang J, Thomassen JQ, Kornhuber J, Haines JL, Vogelgsang J, Pineda JA, Fortea J, Popp J, Deckert J, Buerger K, Morgan K, Fliessbach K, Sleegers K, Molina-Porcel L, Kilander L, Weinhold L, Farrer LA, Wang LS, Kleineidam L, Farotti L, Parnetti L, Tremolizzo L, Hausner L, Benussi L, Froelich L, Ikram MA, Deniz-Naranjo MC, Tsolaki M, Rosende-Roca M, Lowenmark M, Hulsman M, Spallazzi M, Pericak-Vance MA, Esiri M, Bernal Sanchez-Arjona M, Dalmasso MC, Martinez-Larrad MT, Arcaro M, Nothen MM, Fernandez-Fuertes M, Dichgans M, Ingelsson M, Herrmann MJ, Scherer M, Vyhnalek M, Kosmidis MH, Yannakoulia M, Schmid M, Ewers M, Heneka MT, Wagner M, Scamosci M, Kivipelto M, Hiltunen M, Zulaica M, Alegret M, Fornage M, Roberto N, van Schoor NM, Seidu NM, Banaj N, Armstrong NJ, Scarmeas N, Scherbaum N, Goldhardt O, Hanon O, Peters O, Skrobot OA, Quenez O, Lerch O, Bossu P, Caffarra P, Dionigi Rossi P, Sakka P, Mecocci P, Hoffmann P, Holmans PA, Fischer P, Riederer P, Yang Q, Marshall R, Kalaria RN, Mayeux R, Vandenberghe R, Cecchetti R, Ghidoni R, Frikke-Schmidt R, Sorbi S, Hagg S, Engelborghs S, Helisalmi S, Botne Sando S, Kern S, Archetti S, Boschi S, Fostinelli S, Gil S, Mendoza S, Mead S, Ciccone S, Djurovic S, Heilmann-Heimbach S, Riedel-Heller S, Kuulasmaa T, Del Ser T, Lebouvier T, Polak T, Ngandu T, Grimmer T, Bessi V, Escott-Price V, Giedraitis V, Deramecourt V, Maier W, Jian X, Pijnenburg YAL; EADB contributors; GR@ACE study group; DEGESCO consortium; IGAP (ADGC, CHARGE, EADI, GERAD); PGC-ALZ consortia; Kehoe PG, Garcia-Ribas G, Sanchez-Juan P, Pastor P, Perez-Tur J, Pinol-Ripoll G, Lopez de Munain A, Garcia-Alberca JM, Bullido MJ, Alvarez V, Lleo A, Real LM, Mir P, Medina M, Scheltens P, Holstege H, Marquie M, Saez ME, Carracedo A, Amouyel P, Schellenberg GD, Williams J, Seshadri S, van Duijn CM, Mather KA, Sanchez-Valle R, Serrano-Rios M, Orellana A, Tarraga L, Blennow K, Huisman M, Andreassen OA, Posthuma D, Clarimon J, Boada M, van der Flier WM, Ramirez A, Lambert JC, van der Lee SJ, Ruiz A. Author Correction: Common variants in Alzheimer's disease and risk stratification by polygenic risk scores. Nat Commun. 2023 Feb 9;14(1):716. doi: 10.1038/s41467-023-36192-x. No abstract available.

  PMID: 36759603 BACKGROUND

• European Alzheimer's & Dementia Biobank Mendelian Randomization (EADB-MR) Collaboration; Luo J, Thomassen JQ, Bellenguez C, Grenier-Boley B, de Rojas I, Castillo A, Parveen K, Kucukali F, Nicolas A, Peters O, Schneider A, Dichgans M, Rujescu D, Scherbaum N, Jurgen D, Riedel-Heller S, Hausner L, Porcel LM, Duzel E, Grimmer T, Wiltfang J, Heilmann-Heimbach S, Moebus S, Tegos T, Scarmeas N, Clarimon J, Moreno F, Perez-Tur J, Bullido MJ, Pastor P, Sanchez-Valle R, Alvarez V, Boada M, Garcia-Gonzalez P, Puerta R, Mir P, Real LM, Pinol-Ripoll G, Garcia-Alberca JM, Royo JL, Rodriguez-Rodriguez E, Soininen H, Kuulasmaa T, de Mendonca A, Mehrabian S, Hort J, Vyhnalek M, van der Lee S, Graff C, Papenberg G, Giedraitis V, Boland A, Bacq-Daian D, Deleuze JF, Nicolas G, Dufouil C, Pasquier F, Hanon O, Debette S, Grunblatt E, Popp J, Benussi L, Galimberti D, Arosio B, Mecocci P, Solfrizzi V, Parnetti L, Squassina A, Tremolizzo L, Borroni B, Nacmias B, Sorbi S, Caffarra P, Seripa D, Rainero I, Daniele A, Masullo C, Spalletta G, Williams J, Amouyel P, Jessen F, Kehoe P, Tsolaki M, Rossi G, Sanchez-Juan P, Sleegers K, Ingelsson M, Andreassen OA, Hiltunen M, Van Duijn C, Sims R, van der Flier W, Ruiz A, Ramirez A, Lambert JC, Frikke-Schmidt R. Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease. JAMA Netw Open. 2023 May 1;6(5):e2313734. doi: 10.1001/jamanetworkopen.2023.13734.

  PMID: 37195665 BACKGROUND

• Lehmann S, Schraen-Maschke S, Vidal JS, Delaby C, Blanc F, Paquet C, Allinquant B, Bombois S, Gabelle A, Hanon O; The BALTAZAR Study Group. Head-to-Head Comparison of Two Plasma Phospho-tau Assays in Predicting Conversion of Mild Cognitive Impairment to Dementia. Clin Chem. 2023 Sep 1;69(9):1072-1083. doi: 10.1093/clinchem/hvad103.

  PMID: 37654065 BACKGROUND

• Lehmann S, Schraen-Maschke S, Vidal JS, Delaby C, Blanc F, Paquet C, Allinquant B, Bombois S, Gabelle A, Hanon O. Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function. J Neurol Neurosurg Psychiatry. 2023 Jun;94(6):411-419. doi: 10.1136/jnnp-2022-330540. Epub 2023 Apr 3.

  PMID: 37012068 BACKGROUND

• Lehmann S, Schraen-Maschke S, Vidal JS, Allinquant B, Bombois S, Gabelle A, Hanon O. Plasma Abeta42/Abeta40 ratio is independent of renal function. Alzheimers Dement. 2023 Jun;19(6):2737-2739. doi: 10.1002/alz.12949. Epub 2023 Feb 12. No abstract available.

  PMID: 36774628 BACKGROUND

• Lehmann S, Schraen-Maschke S, Vidal JS, Blanc F, Paquet C, Allinquant B, Bombois S, Gabelle A, Delaby C, Hanon O; BALTAZAR Study Group. Blood Neurofilament Levels Predict Cognitive Decline across the Alzheimer's Disease Continuum. Int J Mol Sci. 2023 Dec 11;24(24):17361. doi: 10.3390/ijms242417361.

  PMID: 38139190 BACKGROUND

• Duron E, Vidal JS, Grousselle D, Gabelle A, Lehmann S, Pasquier F, Bombois S, Buee L, Allinquant B, Schraen-Maschke S, Baret C, Rigaud AS, Hanon O, Epelbaum J. Somatostatin and Neuropeptide Y in Cerebrospinal Fluid: Correlations With Amyloid Peptides Abeta1-42 and Tau Proteins in Elderly Patients With Mild Cognitive Impairment. Front Aging Neurosci. 2018 Oct 1;10:297. doi: 10.3389/fnagi.2018.00297. eCollection 2018.

  PMID: 30327597 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction; Dementia; Memory Disorders

Interventions

Biomarkers; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biological Factors; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Olivier Hanon, ph

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2011
• First Posted: March 15, 2011
• Study Start: September 3, 2010
• Primary Completion: February 26, 2015
• Study Completion: March 16, 2018
• Last Updated: September 12, 2025

Record last verified: 2025-09

Locations

FR (1)