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Updated: Apr 26, 2026
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Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration
Published on: January 9, 2020
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Rare Variants and Transcriptomics in Alzheimer disease
Crystal Humphries1, Martin A Kohli2
1Department of Human Genetics, John T. Macdonald Foundation, University of Miami, Miller School of Medicine, 1501 NW 10th Avenue (BRB-531), Miami, FL 33136, USA ; John P. Hussman Institute for Human Genomics (HIHG), University of Miami, Miller School of Medicine, 1501 NW 10th Avenue (BRB-531), Miami, FL 33136, USA.
Current Genetic Medicine Reports
|July 22, 2014
Summary
Genetic studies confirm the amyloid hypothesis for Alzheimer's disease (AD). Rare variants in genes like TREM2 offer new insights into AD mechanisms and potential personalized treatments.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Alzheimer's disease (AD) is a prevalent dementia in older adults, lacking effective treatments.
- Early-onset AD (EOAD) is linked to mutations in APP, PSEN1, and PSEN2 genes.
- Late-onset AD (LOAD) susceptibility is associated with common variants in over 20 genes, notably APOE.
Purpose of the Study:
- To review rare susceptibility variants in LOAD with significant effects.
- To highlight recently identified variants in APP, TREM2, and PLD3 genes.
- To discuss the implications of genetic findings for AD pathogenesis and personalized medicine.
Main Methods:
- Review of human genetic studies, including genome-wide association studies (GWAS).
- Analysis of rare variant data in EOAD and LOAD.
- Integration of transcriptomics data across various tissues.
Main Results:
- Human genetic studies consistently support the amyloid hypothesis for both EOAD and LOAD.
- Identification of rare variants in APP, TREM2, and PLD3 with substantial effects on AD risk.
- Overlapping biological processes (inflammation, cytoskeleton, synapses) identified between genetic and transcriptomic studies.
Conclusions:
- Genetic evidence strongly supports the amyloid cascade hypothesis in Alzheimer's disease.
- Rare variants in specific genes play a significant role in AD pathogenesis.
- Transcriptomic profiles in pre-symptomatic carriers suggest early molecular changes, paving the way for personalized medicine approaches.
Keywords:
APPAlzheimer diseasePLD3PSEN1PSEN2TREM2dementiaelderlylate-onset Alzheimer disease (LOAD)personalized medicinetranscriptomicsMore Related Videos
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