Introduction: Adults with Down syndrome (DS) are at exceptionally high risk for Alzheimer's disease (AD), with virtually all individuals developing key neuropathological features by age 40. Identifying biomarkers of AD progression in DS can provide valuable insights into pathogenesis and suggest targets for disease modifying treatments.
Methods: We describe the development of a multi-center, longitudinal study of biomarkers of AD in DS. The protocol includes longitudinal examination of clinical, cognitive, blood and cerebrospinal fluid-based biomarkers, magnetic resonance imaging and positron emission tomography measures (at 16-month intervals), as well as genetic modifiers of AD risk and progression.
Results: Approximately 400 individuals will be enrolled in the study (more than 370 to date). The methodological approach from the administrative, clinical, neuroimaging, omics, neuropathology, and statistical cores is provided.
Discussion: This represents the largest U.S.-based, multi-site, biomarker initiative of AD in DS. Findings can inform other multidisciplinary networks studying AD in the general population.
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http://dx.doi.org/10.1002/dad2.12065 | DOI Listing |
Acta Neuropathol Commun
January 2025
Department of Biological Sciences, Purdue University, 915 Mitch Daniels Blvd, West Lafayette, IN, USA.
Dementia refers to an umbrella phenotype of many different underlying pathologies with Alzheimer's disease (AD) being the most common type. Neuropathological examination remains the gold standard for accurate AD diagnosis, however, most that we know about AD genetics is based on Genome-Wide Association Studies (GWAS) of clinically defined AD. Such studies have identified multiple AD susceptibility variants with a significant portion of the heritability unexplained and highlighting the phenotypic and genetic heterogeneity of the clinically defined entity.
View Article and Find Full Text PDFNeurotherapeutics
January 2025
Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada. Electronic address:
Amyloidogenic protein aggregation is a pathological hallmark of Alzheimer's Disease (AD). As such, this critical feature of the disease has been instrumental in guiding research on the mechanistic basis of disease, diagnostic biomarkers and preventative and therapeutic treatments. Here we review identified molecular triggers and modulators of aggregation for two of the proteins associated with AD: amyloid beta and tau.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
First Operating Room, The First Hospital of Jilin University, Changchun, China. Electronic address:
Background: Certain peripheral proteins are believed to be involved in the development of Alzheimer's disease (AD), but the roles of other new protein biomarkers are still unclear. Current treatments aim to manage symptoms, but they are not effective in stopping the progression of the disease. New drug targets are needed to prevent Alzheimer's disease.
View Article and Find Full Text PDFMaturitas
January 2025
Institut du Vieillissement, Gérontopôle de Toulouse, Centre Hospitalo-Universitaire de Toulouse, 37 allées Jules Guesde, 31000 Toulouse, France; Institut Hospitalo-Universitaire HealthAge, Cité de la Santé, Place Lange, 31059 Toulouse, France; UMR INSERM, 1295 University of Toulouse III and Faculté de Médecine, 118 Rte de Narbonne, 31062 Toulouse, France.
This four-year longitudinal study investigated whether the cross-sectional and longitudinal associations of inflammation-related and neurodegenerative-related blood biomarkers with intrinsic capacity differ according to sex. The sample comprised 1117 older adults (<70 years, 63.8 % females) from the Multidomain Alzheimer's Prevention Trial (MAPT).
View Article and Find Full Text PDFCNS Neurosci Ther
January 2025
Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Objective: Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are common neurodegenerative diseases with distinct but overlapping pathogenic mechanisms. The clinical similarities between these diseases often result in high misdiagnosis rates, leading to serious consequences. Peripheral blood mononuclear cells (PBMCs) are easy to collect and can accurately reflect the immune characteristics of both DLB and AD.
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