Related Experiment Video
Updated: Aug 16, 2025
09:22
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
18.5K
Polygenic Effect on Tau Pathology Progression in Alzheimer's Disease
Anna Rubinski1, Simon Frerich1,2, Rainer Malik1
1Institute for Stroke and Dementia Research, University Hospital, Ludwig Maximilian University, Munich, Germany.
Annals of Neurology
|December 26, 2022
Summary
A polygenic score (PGS) combining Alzheimer's disease (AD) genetic risk variants predicts faster tau accumulation and cognitive decline. This finding can improve clinical trial efficiency by identifying at-risk individuals.
Area of Science:
- Neuroscience
- Genetics
- Medical Imaging
Background:
- Alzheimer's disease (AD) risk is influenced by polygenic variation.
- The impact of polygenic risk on tau accumulation, a key dementia driver, remains unclear.
Purpose of the Study:
- To investigate the association between a polygenic score (PGS) for AD risk and the rate of fibrillar-tau accumulation.
- To assess the utility of PGS in predicting cognitive decline and enhancing clinical trial design.
Main Methods:
- Generated an AD polygenic score (PGS) using 85 single-nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS).
- Assessed longitudinal tau-PET, amyloid-PET, and cognitive data in 231 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI).
- Utilized PGS and amyloid-PET to predict tau-PET accumulation rates and cognitive decline.
Main Results:
- Higher PGS correlated with increased tau-PET accumulation rates, especially with elevated amyloid-PET.
- Tau-PET increases mediated the relationship between PGS and accelerated cognitive decline.
- Risk enrichment using high PGS demonstrated a 34% reduction in clinical trial sample size requirements.
Conclusions:
- The AD polygenic score effectively predicts tau progression and subsequent cognitive decline.
- PGS can enhance statistical power and efficiency in clinical trials targeting tau pathology.
Related Concept Videos
01:26Alzheimer's Disease: Overview
602
Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
602
01:28Human Genetics
660
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
660
01:22Alzheimer's Disease: Treatment
238
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
238