Genetically identical twins show comparable tau PET load and spatial distribution.

Area of Science:

• Neuroscience
• Genetics
• Alzheimer's Disease Research

Background:

• Tau accumulation in Alzheimer's disease (AD) begins preclinically and correlates with cognitive decline.
• Understanding genetic and environmental factors in tau pathology is crucial for AD prevention.
• Identical twin studies offer insights into genetic versus environmental contributions to disease processes.

Purpose of the Study:

• To investigate similarities and differences in tau load and spatial distribution in genetically identical twin pairs.
• To explore the influence of genetic and environmental factors on tau pathology using 18F-flortaucipir PET imaging.
• To identify potential modifiable environmental factors associated with within-pair tau differences.

Main Methods:

• Studied 78 genetically identical twins (39 pairs) aged 73 ± 6 years, enriched for amyloid-β and APOE ε4.
• Utilized dynamic 18F-flortaucipir Positron Emission Tomography (PET) to measure tau binding potentials (BPND).
• Analyzed within-pair similarities using intra-class correlations and spatial distribution comparisons; explored environmental factor associations.

Main Results:

• Identical twins showed significant similarities in tau load (BPND) in entorhinal, neocortical, and global regions.
• The spatial distribution of tau was significantly more similar between co-twins than non-twin pairs (86% accuracy in pair identification).
• Within-pair differences in tau BPND correlated with differences in depressive symptoms, physical activity, and social activity.

Conclusions:

• Genetic factors play a significant role in Alzheimer's disease tau accumulation and spread, as evidenced by twin similarities.
• Environmental factors, including lifestyle choices, also contribute to variations in tau pathology within identical twin pairs.
• Findings support the potential for modifiable environmental interventions in Alzheimer's disease prevention strategies.