Brain-derived Tau Oligomer Polymorphs: Distinct Aggregations, Stability Profiles, and Biological Activities

Overview

Journal Commun Biol

Date 2025 Jan 14

PMID 39809992

Authors

Filippa Lo Cascio

Suhyeorn Park

Urmi Sengupta

Nicha Puangmalai

Nemil Bhatt

Nikita Shchankin

Cynthia Jerez

Naomi Moreno

Alice Bittar

Rhea Xavier

Yingxin Zhao

Cankun Wang

Hongjun Fu

Qin Ma

Mauro Montalbano

Rakez Kayed

Affiliations

Soon will be listed here.

Abstract

Aggregation of microtubule-associated tau protein is a distinct hallmark of several neurodegenerative disorders such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP). Tau oligomers are suggested to be the primary neurotoxic species that initiate aggregation and propagate prion-like structures. Furthermore, different diseases are shown to have distinct structural characteristics of aggregated tau, denoted as polymorphs. Here, we investigate the structural and functional differences of amplified brain-derived tau oligomers (aBDTOs) from AD, DLB, and PSP. Our results indicate that the aBDTOs possess different structural and morphological features that impact neuronal function, gene regulation, and ultimately disease progression. The distinct tau oligomeric polymorphs may thus contribute to the development of clinical phenotypes and shape the progression of diseases. Our results can provide insight into developing personalized therapy to target a specific neurotoxic tau polymorph.

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