Vascular endothelial growth factor receptor-1 (FLT1) interactions with amyloid-beta in Alzheimer’s disease: A putative biomarker of amyloid-induced vascular damage
We have identified FLT1 as a protein that changes during Alzheimer's disease (AD) whereby higher brain protein levels are associated with more amyloid, more tau, and faster longitudinal cognitive decline. Given FLT1's role in angiogenesis and immune activation, we hypothesized that FLT1 is upregulated in response to amyloid pathology, driving a vascular-immune cascade resulting in neurodegeneration and cognitive decline. We sought to determine (1) if in vivo FLT1 levels (CSF and plasma) associate with biomarkers of AD neuropathology or differ between diagnostic staging in an aged cohort enriched for early disease, and (2) whether FLT1 expression interacts with amyloid on downstream outcomes, such as phosphorylated tau levels and cognitive performance. Additionally, we sought to replicate FLT1 interactions in the brain. The results showed that higher levels of FLT1 in CSF and post-mortem brain tissue related to increased tau, particularly among amyloid positive individuals. These analyses help clarify the potential utility of FLT1 as a biomarker among individuals with evidence of brain amyloidosis.
Authors
- Timothy J. Hohman (ORCID: https://orcid.org/0000-0002-3377-7014)
- David Alan Bennett (ORCID: https://orcid.org/0000-0003-3689-554X)
- Julie A. Schneider (ORCID: https://orcid.org/0000-0002-9482-1752)
- Vladislav Petyuk (ORCID: https://orcid.org/0000-0003-4076-151X)
- Rebecca L. Winfree (ORCID: https://orcid.org/0000-0001-9798-2589)
- Angela Lee Jefferson (ORCID: https://orcid.org/0000-0002-8245-0587)
- Emma Nolan (ORCID: https://orcid.org/0009-0004-9692-0297)
- Kimberly R. Pechman (ORCID: https://orcid.org/0000-0003-0596-8064)
- Henrik Zetterberg (ORCID: https://orcid.org/0000-0003-3930-4354)
- Katherine A. Gifford (ORCID: https://orcid.org/0000-0001-6232-9408)
- Kaj Blennow
Institutions
- Rush University Medical Center (US)
- Pacific Northwest National Laboratory (US)
- Vanderbilt University (US)
- Sahlgrenska University Hospital (SE)
- University College London (GB)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Neurobiology of Aging
- Published
- 2024-12-25
- DOI
- https://doi.org/10.1016/j.neurobiolaging.2024.12.010
- Citations
- 6
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.96
Funders
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Familjen Erling-Perssons Stiftelse
- Cure Alzheimer's Fund
- Stiftelsen för Gamla Tjänarinnor
- EU Joint Programme – Neurodegenerative Disease Research
- National Institute for Health and Care Research
- University College London
- European Commission
- Hjärnfonden
- Vetenskapsrådet
- UK Dementia Research Institute
- HORIZON EUROPE Framework Programme