Associations of the cerebrospinal fluid hepatocyte growth factor with Alzheimer’s disease pathology and cognitive function

Abstract

Background Hepatocyte growth factor (HGF) plays a role in neuronal survival and development, and has been implicated in neurodegenerative diseases. We sought to examine the associations of the CSF HGF with Alzheimer’s disease (AD) pathology and cognitive function. Methods A total of 238 participants (including 90 cognitively normal (CN) and 148 mild cognitive impairment (MCI)) who had measurements of CSF HGF were included from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Multiple linear regression models were utilized to explore the cross-sectional associations of CSF HGF with AD biomarkers (including Aβ42, pTau, and tTau proteins) in non-demented participants. Moreover, linear mixed-effects regression models were utilized to explore the longitudinal associations of HGF subgroups with cognitive function. Mediation analyses were utilized to explore the mediation effects of AD markers. Results MCI individuals had significantly increased CSF HGF compared with the CN individuals. Results of multiple linear regressions showed significant correlations of CSF HGF with CSF Aβ42, pTau, and tTau in non-demented participants. Higher level of baseline CSF HGF was associated with faster cognitive decline. Influences of the baseline CSF HGF on cognition were partially mediated by Aβ42, pTau, and tTau pathologies. Conclusions High concentrations of HGF in CSF may be related to faster cognitive decline. The cognitive consequences of higher CSF HGF partly stem from AD pathology, which suggests that the CSF HGF may be an attractive biomarker candidate to track AD progression.

Global analysis of the heparin-enriched plasma proteome captures matrisome-associated proteins in Alzheimer’s disease

“…Notably, the new database search output of 456 brain samples across Banner and ROSMAP using FragPipe was able to identify 10% more proteins that were associated with M42. Other newly identified members of M42 include SMOC2 and HGF, which have also been shown to be elevated in AD CSF [64][65][66] . Consequently, our findings suggest that both SMOC1 and SMOC2 exhibit elevated levels in the brain and plasma of individuals with AD.…”

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

“…TAB2 [131], LMNA (lamin A/C) [330], HGF (hepatocyte growth factor) [494] and CCL5 [486] migt play an important role in the occurrence and development of obesity. CFTR (CF transmembrane conductance regulator) [380], RHOB (ras homolog family member B) [396], LMNA (lamin A/C) [388], HGF (hepatocyte growth factor) [371], CCL5 [360] and NGFR (nerve growth factor receptor) [383] were altered expression in the Alzheimer’s Disease. CFTR (CF transmembrane conductance regulator) [551], LMNA (lamin A/C) [558], ERBB3 [331], HGF (hepatocyte growth factor) [494], CCL5 [540] and NGFR (nerve growth factor receptor) [554] have been demonstrated to accelerate hypertension progression.…”

Cyanidin 3-Glucoside Induces Hepatocyte Growth Factor in Normal Human Dermal Fibroblasts through the Activation of β2-Adrenergic Receptor

“… 6 , 7 Some reports also highlighted the therapeutic potential of HGF in neuronal diseases such as amyotrophic lateral sclerosis and Alzheimer’s disease by demonstrating that exogenous expression of HGF-regulated neuronal cell survival. 8 , 9 These studies motivate us to search the small molecules that function as HGF inducers for potential therapeutic tools.…”

“…In the normal state, active HGF binds to its receptor, c -Met, and stimulates various biological responses such as proliferation, cell survival, morphogenesis, motility, and angiogenesis. , Therefore, HGF is recognized as a potential therapeutic agent for various diseases, especially hepatic and renal fibrosis and cardiovascular diseases . Moreover, migration and proliferation of keratinocytes can be stimulated by HGF, suggesting the involvement in cutaneous physiology and wound healing. , Some reports also highlighted the therapeutic potential of HGF in neuronal diseases such as amyotrophic lateral sclerosis and Alzheimer’s disease by demonstrating that exogenous expression of HGF-regulated neuronal cell survival. , These studies motivate us to search the small molecules that function as HGF inducers for potential therapeutic tools.…”