Molecular Basis of Tau Protein Misfolding in Alzheimer’s Patients

Faculty: Sivaprakasam Ramamoorthy (CBR) & Nikhil Gandasi (DBG)

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder, accounting for over 70% of dementia cases worldwide. AD is characterized by progressive neurodegeneration along with the aggregation of amyloid and tau proteins. Tau pathology, in the form of neurofibrillary tangles, strongly correlates with cognitive decline. Tau accumulation begins in the entorhinal cortex, spreads to the limbic regions, and subsequently progresses to the neocortical areas, leading to worsening cognitive impairment. While tau aggregation is a hallmark of Alzheimer’s, the exact mechanisms by which tau tangles form and contribute to cell death remain poorly understood. Furthermore, the mechanisms underlying tau propagation are not fully elucidated. Tau is a promising candidate for an early biomarker of Alzheimer’s, but its precise role in disease progression is not yet fully defined. The objective of this proposal is to gain a deeper understanding of the nature of tau fibrils and how they misfold in AD patients.

Siva’s Lab: The student will primarily conduct research in Siva’s lab, focusing on the misfolding of tau proteins.

Nikhil’s Lab: Specializing in live imaging, Nikhil’s lab will offer valuable insights into the trafficking of tau proteins.