Citations 2
Pathogenic variants in the Longitudinal Early‐onset Alzheimer's Disease Study cohort
Jackson, Trever, Rumbaugh, Malia, Eloyan, Ani , Abreu, Marco , Dage, Jeffrey L. , Snoddy, Casey, Faber, Kelley , Hammers, Dustin B. , Taurone, Alexander, Thangarajah, Maryanne, Aisen, Paul, Kramer, Joel H. , Kukull, Walter A. , Vemuri, Prashanthi , Day, Gregory S. , Duara, Ranjan , Graff‐Radford, Neill R. , Masdeu, Joseph C. , Mendez, Mario F. , Onyike, Chiadi U. , Riddle, Meghan , Rogalskı, Emily , Salloway, Stephen , Sha, Sharon J. , Turner, Raymond Scott , Wingo, Thomas S. , Carrillo, María C. , Rabinovici, Gil D. , Apostolova, Liana G. , Vemuri, Prashanthi , Day, Gregory S , Rabinovici, Gil D , Wingo, Thomas S , Dage, Jeffrey L , Nudelman, Kelly , Foroud, Tatiana , Hammers, Dustin B , Beckett, Laurel , Koeppe, Robert A. , Murray, Melissa E. , Toga, Arthur W. , Atri, Alireza , Duara, Ranjan , Honig, Lawrence S. , Jones, David T. , Masdeu, Joseph C , Musiek, Erik , Wolk, David A. , Dickerson, Bradford Clark
Alzheimer's & Dementia | October 7, 2023 | Volume: 19 | Issue: S9 | Pages: No page available
AbstractIntroductionOne goal of the Longitudinal Early‐onset Alzheimer's Disease Study (LEADS) is to investigate the genetic etiology of early onset (40–64 years) cognitive impairment. Toward this goal, LEADS participants are screened for known pathogenic variants.MethodsLEADS amyloid‐positive early‐onset Alzheimer's disease (EOAD) or negative early‐onset non‐AD (EOnonAD) cases were whole exome sequenced (N = 299). Pathogenic variant frequency in APP, PSEN1, PSEN2, GRN, MAPT, and C9ORF72 was assessed for EOAD and EOnonAD. Gene burden testing was performed in cases compared to similar‐age cognitively normal controls in the Parkinson's Progression Markers Initiative (PPMI) study.ResultsPreviously reported pathogenic variants in the six genes were identified in 1.35% of EOAD (3/223) and 6.58% of EOnonAD (5/76). No genes showed enrichment for carriers of rare functional variants in LEADS cases.DiscussionResults suggest that LEADS is enriched for novel genetic causative variants, as previously reported variants are not observed in most cases.Highlights Sequencing identified eight cognitively impaired pathogenic variant carriers. Pathogenic variants were identified in PSEN1, GRN, MAPT, and C9ORF72. Rare variants were not enriched in APP, PSEN1/2, GRN, and MAPT. The Longitudinal Early‐onset Alzheimer's Disease Study (LEADS) is a key resource for early‐onset Alzheimer's genetic research
Cerebrospinal fluid biomarkers in the Longitudinal Early‐onset Alzheimer's Disease Study
Dage, Jeffrey L. , Eloyan, Ani , Thangarajah, Maryanne, Hammers, Dustin B. , Fagan, Anne M. , Gray, Julia, Snoddy, Casey, Faber, Kelley , Foroud, Tatiana M., Aisen, Paul , Griffin, Percy , Grinberg, Lea T. , Kirby, Kala, Kramer, Joel H. , Kukull, Walter A. , Joie, Renaud La , Mundada, Nidhi S. , Rumbaugh, Malia, Soleimani‐Meigooni, David N. , Touroutoglou, Alexandra , Vemuri, Prashanthi , Day, Gregory S. , Graff‐Radford, Neill R. , Duara, Ranjan , Masdeu, Joseph C. , Mendez, Mario F. , Onyike, Chiadi U. , Riddle, Meghan , Rogalskı, Emily , Salloway, Stephen , Sha, Sharon J. , Turner, Raymond Scott , Wingo, Thomas S. , Carrillo, María C. , Rabinovici, Gil D. , Apostolova, Liana G. , Vemuri, Prashanthi , Day, Gregory S , La Joie, Renaud , Grinberg, Lea , Rabinovici, Gil D , Wingo, Thomas S , Dage, Jeffrey L , Hammers, Dustin B , Schindler, Suzanne E. , Nudelman, Kelly , Iaccarino, Leonardo , Kirby, Kala, Koeppe, Robert A. , Murray, Melissa E. , Toga, Arthur W. , Atri, Alireza , Beckett, Laurel , Duara, Ranjan , Honig, Lawrence S. , Jones, David T. , Masdeu, Joseph C , Musiek, Erik , Wolk, David A. , Womack, Kyle , Dickerson, Bradford Clark
Alzheimer's & Dementia | July 25, 2023 | Volume: 19 | Issue: S9 | Pages: No page available
AbstractIntroductionOne goal of the Longitudinal Early Onset Alzheimer's Disease Study (LEADS) is to define the fluid biomarker characteristics of early‐onset Alzheimer's disease (EOAD).MethodsCerebrospinal fluid (CSF) concentrations of Aβ1‐40, Aβ1‐42, total tau (tTau), pTau181, VILIP‐1, SNAP‐25, neurogranin (Ng), neurofilament light chain (NfL), and YKL‐40 were measured by immunoassay in 165 LEADS participants. The associations of biomarker concentrations with diagnostic group and standard cognitive tests were evaluated.ResultsBiomarkers were correlated with one another. Levels of CSF Aβ42/40, pTau181, tTau, SNAP‐25, and Ng in EOAD differed significantly from cognitively normal and early‐onset non‐AD dementia; NfL, YKL‐40, and VILIP‐1 did not. Across groups, all biomarkers except SNAP‐25 were correlated with cognition. Within the EOAD group, Aβ42/40, NfL, Ng, and SNAP‐25 were correlated with at least one cognitive measure.DiscussionThis study provides a comprehensive analysis of CSF biomarkers in sporadic EOAD that can inform EOAD clinical trial design.