Unveiling FAD 3T : A Groundbreaking Transgenic Mouse Model for Accelerating Alzheimer's Disease Research
Year: 2025
Type: article
Abstract: Background Alzheimer's disease (AD) poses a significant challenge in contemporary healthcare, with traditional mouse models often exhibiting prolonged disease progression periods that impede efficient pharmaceutical drug discovery and development. Methods To address this challenge, we developed the FAD 3T transgenic mouse model, incorporating three mutations (hAPP, hPSEN1, hMAPT) that closely replicate key genetic factors implicated in AD pathogenesis. Results The FAD 3T model exhibits phenotypic parallels to human AD patients, with early onset of pathogenic markers. Notably, diagnostic blood markers such as p ‐Tau181, p ‐Tau217, Aβ42/40, and neurofilament light chain (NfL) are detectable in the plasma of 1‐month‐old FAD 3T mice. Elevated levels of phosphorylated Tau (Thr181) are observed in the brain at 1 month of age. Subsequent observations include Aβ deposition and elevated levels of Phospho‐Tau (Thr217, Thr231) at 2 months, followed by elevated levels of Phospho‐Tau (Ser396, Ser202, Thr205) at 3 months, with all markers progressively intensifying with age. Importantly, cognitive deficits, including spatial learning and memory impairments, manifest at earlier stages in these mice. Conclusion Our findings highlight the exceptional fidelity of the FAD 3T model in recapitulating the complex etiology of AD. Compared to traditional AD mouse models, FAD 3T exhibits accelerated disease onset and progression, providing a rapid platform for expediting drug testing cycles, particularly for therapies targeting disease progression. This innovative mouse model represents a transformative tool for enhancing our understanding of AD pathophysiology and facilitating the expedited development of therapeutic strategies.
Source: Alzheimer s & Dementia
Authors: Ziying Lai, Bingzhou Han, Tao Wang, Xiang Gao, Rui Feng
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
OpenAlex ID: W7117101641