Dataset Information

The Longitudinal Early-onset Alzheimer's Disease Study (LEADS): Framework and methodology.

ABSTRACT: Patients with early-onset Alzheimer's disease (EOAD) are commonly excluded from large-scale observational and therapeutic studies due to their young age, atypical presentation, or absence of pathogenic mutations. The goals of the Longitudinal EOAD Study (LEADS) are to (1) define the clinical, imaging, and fluid biomarker characteristics of EOAD; (2) develop sensitive cognitive and biomarker measures for future clinical and research use; and (3) establish a trial-ready network. LEADS will follow 400 amyloid beta (Aβ)-positive EOAD, 200 Aβ-negative EOnonAD that meet National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) or AD dementia, and 100 age-matched controls. Participants will undergo clinical and cognitive assessments, magnetic resonance imaging (MRI), [¹⁸ F]Florbetaben and [¹⁸ F]Flortaucipir positron emission tomography (PET), lumbar puncture, and blood draw for DNA, RNA, plasma, serum and peripheral blood mononuclear cells, and post-mortem assessment. To develop more effective AD treatments, scientists need to understand the genetic, biological, and clinical processes involved in EOAD. LEADS will develop a public resource that will enable future planning and implementation of EOAD clinical trials.

SUBMITTER: Apostolova LG

PROVIDER: S-EPMC8939858 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

The Longitudinal Early-onset Alzheimer's Disease Study (LEADS): Framework and methodology.

Apostolova Liana G LG Aisen Paul P Eloyan Ani A Fagan Anne A Fargo Keith N KN Foroud Tatiana T Gatsonis Constantine C Grinberg Lea T LT Jack Clifford R CR Kramer Joel J Koeppe Robert R Kukull Walter A WA Murray Melissa E ME Nudelman Kelly K Rumbaugh Malia M Toga Arthur A Vemuri Prashanthi P Trullinger Amy A Iaccarino Leonardo L Day Gregory S GS Graff-Radford Neill R NR Honig Lawrence S LS Jones David T DT Masdeu Joseph J Mendez Mario M Musiek Erik E Onyike Chiadi U CU Rogalski Emily E Salloway Steve S Wolk David A DA Wingo Thomas S TS Carrillo Maria C MC Dickerson Bradford C BC Rabinovici Gil D GD

Alzheimer's & dementia : the journal of the Alzheimer's Association 20210521 12

Patients with early-onset Alzheimer's disease (EOAD) are commonly excluded from large-scale observational and therapeutic studies due to their young age, atypical presentation, or absence of pathogenic mutations. The goals of the Longitudinal EOAD Study (LEADS) are to (1) define the clinical, imaging, and fluid biomarker characteristics of EOAD; (2) develop sensitive cognitive and biomarker measures for future clinical and research use; and (3) establish a trial-ready network. LEADS will follow ...[more]

PMID: 34018654

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Project description:IntroductionSequencing efforts to identify genetic variants and pathways underlying Alzheimer's disease (AD) have largely focused on late-onset AD although early-onset AD (EOAD), accounting for ∼10% of cases, is largely unexplained by known mutations, resulting in a lack of understanding of its molecular etiology.MethodsWhole-genome sequencing and harmonization of clinical, neuropathological, and biomarker data of over 5000 EOAD cases of diverse ancestries.ResultsA publicly available genomics resource for EOAD with extensive harmonized phenotypes. Primary analysis will (1) identify novel EOAD risk loci and druggable targets; (2) assess local-ancestry effects; (3) create EOAD prediction models; and (4) assess genetic overlap with cardiovascular and other traits.DiscussionThis novel resource complements over 50,000 control and late-onset AD samples generated through the Alzheimer's Disease Sequencing Project (ADSP). The harmonized EOAD/ADSP joint call will be available through upcoming ADSP data releases and will allow for additional analyses across the full onset range.HighlightsSequencing efforts to identify genetic variants and pathways underlying Alzheimer's disease (AD) have largely focused on late-onset AD although early-onset AD (EOAD), accounting for ∼10% of cases, is largely unexplained by known mutations. This results in a significant lack of understanding of the molecular etiology of this devastating form of the disease. The Early-Onset Alzheimer's Disease Whole-genome Sequencing Project is a collaborative initiative to generate a large-scale genomics resource for early-onset Alzheimer's disease with extensive harmonized phenotype data. Primary analyses are designed to (1) identify novel EOAD risk and protective loci and druggable targets; (2) assess local-ancestry effects; (3) create EOAD prediction models; and (4) assess genetic overlap with cardiovascular and other traits. The harmonized genomic and phenotypic data from this initiative will be available through NIAGADS.

Dataset Information

The Longitudinal Early-onset Alzheimer's Disease Study (LEADS): Framework and methodology.

Publications

The Longitudinal Early-onset Alzheimer's Disease Study (LEADS): Framework and methodology.

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