Abstract previously featured at FENS regional meeting Oslo 2025
Alzheimer’s disease (AD) is the most common form of dementia and currently has no definite cure. Early diagnosis is crucial for providing timely support and treatment options to patients and their families. Traditional diagnostic methods rely on a clinical assessment and A-beta- and Tau-isoforms as biomarkers, which at best offer a yes/no answer, but often only a risk assessment.
AD is a complex neurodegenerative disorder, and its molecular mechanisms across different brain regions and disease stages remain incompletely understood, particularly regarding how neuronal degeneration in one region affects connected areas. AD typically begins with changes in the entorhinal Cortex (EC), one of the first brain regions affected by the accumulation of pathological proteins and neurodegenerative changes. The EC communicates with the CA1 region of the hippocampus via direct connections, with neurons from the lateral EC (LEC) predominantly projecting to the distal region of CA1 (CA1d) and medial EC (MEC) predominantly projecting to the proximal region of CA1 (CA1p). Damage to these neural circuits contributes to early memory impairments.
Here, we investigate in an AD mouse model (APP/PS1, C57BL/6J) if the transcriptomes of the proximal versus distal CA1 subregion of the hippocampus are differentially altered in wildtype versus transgenic mice. We think that disturbed neuronal integrity and activity in one brain region leads to disturbed transcription in a different brain region connected to the first. A deeper network-based understanding of the disease at a molecular level may lead to the identification of new drug targets, biomarkers, and more precise diagnostic approaches.