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MHC class I molecules regulate brain development and plasticity in mice and HLA class I molecules are associated with brain disorders in humans. We investigated the relationship between plasma-derived soluble human HLA class I molecules (sHLA class I), HLA class I serotypes and dementia. A cohort of HLA class I serotyped elderly subjects with no dementia/pre-dementia (NpD, n = 28), or with dementia (D, n = 28) was studied. Multivariate analysis was used to examine the influence of dementia and HLA class I serotype on sHLA class I levels, and to compare sHLA class I within four groups according to the presence or absence of HLA-A23/A24 and dementia. HLA-A23/A24 and dementia, but not age, significantly influenced the level of sHLA class I. Importantly, the concurrent presence of HLA-A23/A24 and dementia was associated with higher levels of sHLA class I (p < 0.001). This study has shown that the simultaneous presence of HLA-A23/HLA-A24 and dementia is associated with high levels of serum sHLA class I molecules. Thus, sHLA class I could be considered a biomarker of neurodegeneration in certain HLA class I carriers., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Blood biomarkers can improve the ability to diagnose dementia, providing new information to better understand the pathophysiology and causes of the disease. Some studies with patients have already shown changes in metabolic profiles among patients with pathological cognitive decline or Alzheimer's disease, when compared to individuals with normal cognition. To search for new metabolic biomarkers of dementia, we analyzed serum levels of several metabolites, measured by nuclear magnetic resonance spectroscopy, in elderly individuals, a group with normal cognitive decline (control), and three other groups with cognitive decline. pathological (low, moderate, and severe). Decreased plasma levels of tyrosine, glutamate, valine, leucine, and isoleucine are associated with worsening of pathological cognitive decline. However, the area under analysis of receptor operating characteristics suggests that tyrosine and glutamate have low specificity and sensitivity. Valine, leucine, and isoleucine are influenced by blood glucose or diabetes, but these conditions do not seem to be of great influence in the differences observed. Isobutyrate, histidine, acetone and unknown-1 metabolite also decrease their plasma levels with increasing CD. Isobutyrate ad histidine could have neuroprotective and antioxidant actions, respectively. To elucidate the role of decreased unknown metabolite-1 as a CD biomarker, it will be necessary to previously investigate its identity. To define and elucidate the role of acetone in pathological CD, additional laboratory and clinical studies must be performed. All these metabolites together may constitute a set of biomarkers with capability to identify pathological CD or dementia. Decrease of glutamate, tyrosine, valine, leucine, isoleucine, histidine, isobutyrate, acetone and unknown-1 metabolite together are a set of biomarkers able to identify pathological CD or dementia. Histidine, isobutyrate, acetone and unknown-1 metabolite are more specific biomarkers of CD. [Display omitted] • Glutamate, valine, leucine, isoleucine, isobutyrate, histidine, acetone and unknown-1 metabolite are associated to CD or dementia. • Valine, leucine, and isoleucine (BCAA) are also slightly influenced by glycemia changes. • Glutamate, isobutyrate, and histidine were associated to pathways involved in neurodegeneration. • The role of acetone in CD changes and identity of unknown-1 metabolite must be truly analyzed. [ABSTRACT FROM AUTHOR]