Cerebrospinal fluid heart fatty acid-binding protein as a predictive biomarker of neurodegeneration in Alzheimer's disease

Objective:This study aims to investigate whether the heart fatty acid-binding protein(HFABP)in the cerebrospinal fluid(CSF)was a potential predictive biomarker for Alzheimer’s disease(AD).Methods:We evaluated the associations of CSF HFABP levels with core biomarkers,cognition,and brain structure in a sample population(n=302)from the Alzheimer’s Disease Neuroimaging Initiative(ADNI)database.Multiple linear regression and mixed-effects models were employed in the analyses.AD progression was assessed using the Kaplan–Meier survival analysis.Results:CSF HFABP was higher in patients with mild cognitive impairment and AD than the normal controls(p<0.001)and was particularly higher in those with amyloid-β(Aβ)pathologic features.CSF HFABP was associated with higher baseline CSF t-tau(p<0.001),CSF p-tau(p<0.001),and CSF t-tau/Aβ42 and CSF p-tau/Aβ42(p<0.01).Moreover,CSF HFABP was found to play predictive roles in hippocampal atrophy(p<0.01),cognitive decline(p<0.05),and the risk of AD(p<0.001).Conclusion:Our findings suggest that CSF HFABP can be a predictive biomarker of AD.

Cortical and Subcortical Grey Matter Abnormalities in White Matter Hyperintensities and Subsequent Cognitive Impairment

Grey matter(GM)alterations may contribute to cognitive decline in individuals with white matter hyperintensities(WMH)but no consensus has yet emerged.Here,we investigated cortical thickness and grey matter volume in 23 WMH patients with mild cognitive impairment(WMH-MCI),43 WMH patients without cognitive impairment,and 55 healthy controls.Both WMH groups showed GM atrophy in the bilateral thalamus,fronto-insular cortices,and several parietal-temporal regions,and the WMH-MCI group showed more extensive and severe GM atrophy.The GM atrophy in the thalamus and fronto-insular cortices was associated with cognitive decline in the WMH-MCI patients and may mediate the relationship between WMH and cognition in WMH patients.Furthermore,the main results were well replicated in an independent dataset from the Alzheimer's Disease Neuroimaging Initiative database and in other control analyses.These comprehensive results provide robust evidence of specific GM alterations underlying WMH and subsequent cognitive impairment.