Background: In this introductory talk, we embark on a journey of through the genomic frontiers of Alzheimer's research via the revolutionary Alzheimer's Disease Sequencing Project (ADSP).
Method: ADSP integrates together various components that collectively unravel the intricate genetic landscape of Alzheimer's disease with the ultimate goal of advancing precision medicine for the millions affected globally by this devastating disease. With a goal of sequencing and analyzing up to 150,000 complete genomes and associated clinical and functional data in the next five years, ADSP has amassed an unprecedented wealth of genomic data from diverse populations, providing a comprehensive and holistic understanding of the genetic underpinnings of Alzheimer's disease.
Result: This presentation serves as a primer, exploring various components of the ADSP and discuss the unprecedented opportunities it presents for Alzheimer's disease and AI/ML researchers: (1) Diversity Initiative: The ADSP places a paramount emphasis on diversity, ensuring the inclusion of a wide range of populations in its genomic dataset. (2) Phenotype Harmonization: Harmonizing phenotypic data across diverse cohorts is a critical aspect of the ADSP, facilitating meaningful comparisons and analyses. (3) Functional Genomics: Moving beyond genetic variations, the ADSP incorporates functional genomics to discern the biological mechanisms at play. (4) AI/ML Opportunities: the focus of this session, we will start by illuminating the wide range of opportunities the ADSP offers to AI/ML researchers. From predictive modeling to identifying novel biomarkers and therapeutic targets, we will explore the vast landscape of possibilities for data-driven discoveries that can shape the future of Alzheimer's research and precision medicine.
Conclusion: As we uncover the potential of AI/ML within the ADSP, we will emphasize the need for collaborative initiatives between AI/ML researchers and the broader Alzheimer's research community. The synergy between these fields holds the key to unlocking breakthroughs that can translate genomic insights into tangible clinical advancements.
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http://dx.doi.org/10.1002/alz.087888 | DOI Listing |
Adv Sci (Weinh)
January 2025
School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
β-secretase (BACE1) is instrumental in amyloid-β (Aβ) production, with overexpression noted in Alzheimer's disease (AD) neuropathology. The interaction of Aβ with the receptor for advanced glycation endproducts (RAGE) facilitates cerebral uptake of Aβ and exacerbates its neurotoxicity and neuroinflammation, further augmenting BACE1 expression. Given the limitations of previous BACE1 inhibition efforts, the study explores reducing BACE1 expression to mitigate AD pathology.
View Article and Find Full Text PDFActa 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 PDFNeuroscience
January 2025
Departamento de Genómica, Instituto de Investigaciones Biológicas Clemente Estable, MEC, Av. Italia 3318, Montevideo, CP 11600, Uruguay; Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Iguá, Montevideo, 4225, CP 11400, Uruguay. Electronic address:
Local protein synthesis (LPS) in axons is now recognized as a physiological process, participating both in the maintenance of axonal function and diverse plastic phenomena. In the last decades of the 20th century, the existence and function of axonal LPS were topics of significant debate. Very early, axonal LPS was thought not to occur at all and was later accepted to play roles only during development or in response to specific conditions.
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