Heart-type fatty acid binding protein and vascular endothelial growth factor: cerebrospinal fluid biomarker candidates for Alzheimer’s disease

Abstract

The main objective of the study was to validate the findings of previous cerebrospinal fluid (CSF) proteomic studies for the differentiation between Alzheimer's disease (AD) dementia and physiological ageing. The most consistently significant proteins in the separation between AD dementia versus normal controls using CSF proteomics were identified in the literature. The classification performance of the four pre-selected proteins was explored in 92 controls, 149 patients with mild cognitive impairment (MCI), and 69 patients with AD dementia. Heart-type fatty acid binding protein (hFABP) and vascular endothelial growth factor (VEGF) CSF concentrations distinguished between healthy controls and patients with AD dementia with a sensitivity and specificity of 57 and 35%, and 76 and 84%, respectively. The optimal classification was achieved by a combination of the two additional CSF biomarker candidates in conjunction with the three established markers Amyloid-β (Aβ)1-42, total-Tau (tTau), and phosphorylated-Tau (pTau)181, which resulted in a sensitivity of 83% and a specificity of 86%. hFABP also predicted the progression from MCI to AD dementia. The present study provides evidence in support of hFABP and VEGF in CSF as AD biomarker candidates to be used in combination with the established markers Aβ1-42, tTau, and pTau181.

Cerebrospinal fluid biomarkers of Alzheimer’s disease

“…The study by Guo et al supports the potential of hFABP and VEGF in CSF as AD biomarkers in combination with Aβ42, t-tau, and p-tau181 [89] . precursor, Aβ, apolipoprotein E precursor, serum albumin precursor, keratin type I cytoskeletal 9, and tetranectin) was able to discriminate AD patients from controls with a median accuracy of 95% (sensitivity 85% and specificity 97%) [90] .…”

Gnetol, a Resveratrol Derivative Ameliorates Malathion-Induced Neurotoxicity through Modulating Lysosomal Membrane Permeabilization in N2a Cells

“…Recently, factors such as heart-type fatty acid binding protein (hFABP) and vascular endothelial growth factor can be a one of important biomarkers in hallmark of AD and other dementias [27]. Amyloid β and phosphorylated tau have been studied to elucidate the mechanism of action of neurodegeneration.…”

Genetic resilience to amyloid related cognitive decline

“…This discrepancy may be due, in part, to the fact that there is mixed epidemiological evidence of risk and resilience when measuring VEGF. High levels of serum VEGF have been associated with an increased risk of stroke (Pikula et al, 2013) and more frequent cerebral microbleeds among individuals with Alzheimer's disease (Zhang et al, 2016), while CSF VEGF levels have been reported to be higher (Tarkowski et al, 2002), lower (Guo, Alexopoulos, & Perneczky, 2013), and equivalent (Blasko et al, 2006) among individuals with AD compared to controls. Perhaps VEGF-related genes like PROK1 will provide clues to help unravel the complex associations among VEGF, cerebrovascular disease, and AD.…”