Vascular endothelial growth factor receptor-1 (FLT1) interactions with amyloid-beta in Alzheimer’s disease: A putative biomarker of amyloid-induced vascular damage
Year: 2024
Type: article
Study design: Observational Study
Abstract: 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. • Endothelial cell dysfunction and cerebrovascular injury in Alzheimer's disease. • FLT1 expression relates to Alzheimer’s disease progression through amyloid and tau. • Cerebrospinal fluid and plasma FLT1 measures relate to worse neuropathology. • FLT1 upregulated in response to amyloid and is driver of tau pathology in brain.
Source: Neurobiology of Aging
Institutions: Vanderbilt University Medical Center, Vanderbilt University, Sahlgrenska University Hospital, University of Gothenburg, University of Wisconsin–Madison, UK Dementia Research Institute, University of Wisconsin Health, University College London, Rush University Medical Center, Pacific Northwest National Laboratory
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,330
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, Olav Thon Stiftelsen, National Institutes of Health, Horizon 2020 Framework Programme, HORIZON EUROPE Framework Programme, National Institute on Aging, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development, H2020 Marie Skłodowska-Curie Actions
Awards: G1057200632, G1069732457, G1088883541, G1251185638, G1282666458, G150733400, G1513904913, G1551449788, G1588116593, G1771944843, G1802301745, G1833008592, G201353144, G2057385626, G2200385677, G237833635, Genetic Drivers of Resilience to Alzheimer's Disease, G249615658, G2543812357, G266544023, G2799940023, G2830398374, G289101313, G292763017, G3159755494, G3241251457, Fluid biomarkers for neurodegenerative dementias, G3743240706, Pathway discovery, validation and compound identification for Alzheimer's disease, G3903502641, G3914690605, G4019563118, G4234328627, G4260843567, Neuroprotective Effects of Vascular Endothelial Growth Factor in Alzheimer's Disease, G432431387, G434337789, G4377393254, G4421368135, G4505337483, Risk Factors, Pathology, and Clinical Expressions of AD, G4970245363, G5005653641, G5040492720, G506008078, G516766298, Fluid biomarkers for neurodegenerative dementias, CASCADE: CAuSe or Consequence in Alzheimer DiseasE?, G6158734006, Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis, G6289970089, G6399140587, Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis, Left Ventricular Function and Mild Cognitive Impairment, G6720674715, G6745400708, G691317373, G828200374, G860030259, Vanderbilt Memory & Aging Project, G983864884
OpenAlex ID: W4405774645