The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)
Cross-Seeding Potential of Misfolded Amyloid-beta Strains on Tau Protein: Examining the Puzzle Pieces of Alzheimer's Disease
Author ORCID Identifier
Date of Graduation
Masters of Science (MS)
Rodrigo Morales, PhD
Andrey Tsvetkov, PhD
Sheng Zhang, PhD
Assaf Gottlieb, PhD
Akihiko Urayama, PhD
Alzheimer’s disease (AD) is a neurodegenerative disorder that will progressively impair cognitive function. AD is the leading source of dementia, and affects one third of the senior citizens in the United States. Aging is the primary risk factor for AD and due to the expected rise in human lifespan worldwide, the occurrence rate of AD diagnosis is projected to increase. This observation is increasingly alarming when considering there is no treatment for reversal or prevention of AD yet.
AD is characterized by gross pathological hallmarks in the brain. These include the extracellular accumulation of misfolded amyloid-beta (Aβ) and the intraneuronal buildup of tau neurofibrillary tangles (NFTs). Compelling evidence suggests that Aβ triggers tau accumulation. Both of these disease-associated proteins are known to contribute to the typical AD associated clinical signs. Interestingly, these proteins have been shown to display several features similar to those seen in infectious prions, such as their conformational strain diversity. Prion strains trigger diseases that may substantially vary in their pathological and clinical aspects. One example of strain diversity in Aβ can be found in the synthetic 2F and 3F fibrils. These aggregates were originally generated by Petkova et al. by modifying protein aggregation protocols. These strains were thoroughly characterized by their structural features, convincingly showing that misfolded Aβ can adopt different conformations. This paper explores Aβ seed strains differentially influencing the conformation of tau aggregates in order to promote altered tau pathology.
Alzheimer's, Prion, Protein Misfolding, Cross-Seeding