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AD-LINK: Reversing Early Aβ-Driven Network Hyperexcitability

Objective

Despite decades of research, there is currently no drug capable of preventing Alzheimer’s disease (AD), and ~99% of the drug candidates ultimately fail in clinical trials. This high failure rate is largely due to the lack of reliable preclinical models that enable continuous, longitudinal testing of therapeutic interventions from the earliest, pre-symptomatic stages of the disease.

AD‑LINK is a chronic neurotechnology platform designed to extract high‑resolution neurophysiological signatures of early AD across development and disease progression for longitudinal drug testing. Building on ERC‑funded discoveries showing that microglial dysfunction drives early network hyperexcitability, AD‑LINK addresses a fundamental limitation of current methods: no existing tool can provide stable, months‑long high‑density recordings while also enabling precise, localized perturbation of disease‑relevant pathways in freely moving animals. To meet the distinct needs of different disease stages, we will develop two complementary devices: (1) an ultra‑lightweight Neuropixels 2.0 drive for juvenile mice, enabling continuous tracking of the earliest circuit abnormalities during developmental onset; and (2) an integrated Liquid‑Ephys drive for adult mice, combining high‑density electrophysiology with controlled in situ delivery of soluble factors, allowing causal testing of how targeted interventions modulate — and potentially reverse — pathological circuit states. Through iterative engineering, in vivo validation, IP development, and structured engagement with industrial partners, this ERC PoC will deliver a de‑risked research platform that replaces insensitive behavioral endpoints with precise circuit‑level signatures. By enabling longitudinal, mechanistic analysis of early neuronal dysfunction and its modulation over time, AD‑LINK will strengthen the translational foundations of pre‑clinical AD research, thus aiming to increase success rate of AD drug candidates at clinical trials.

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Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

(opens in new window) ERC-2026-POC

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Host institution

VIB VZW
Net EU contribution
€ 150 000,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium
Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
Links
Total cost
No data

Beneficiaries (1)