Homocysteic Acid in Blood Can Detect Mild Cognitive Impairment: A Preliminary Study

Abstract

Background: In the treatment of Alzheimer’s disease (AD), it is thought to be most effective to intervene at the earliest and mildest stages. For diagnosis at the earliest and mildest stages, it is desirable to use a biomarker that can be detected by a minimally invasive, cost-effective technique. Recent research indicates the potential clinical usefulness of plasma amyloid-β (Aβ) biomarkers in predicting brain Aβ burden at an individual level. However, it is as yet unproven that accumulation of Aβ necessarily leads to the development of AD. Objective: Homocysteic acid (HCA) is useful as an early diagnostic marker for mild cognitive impairment (MCI), a pre-stage of AD. Methods: We measured the concentration of HCA, tumor necrosis factor alpha, cortisol, tau, and phosphorylated tau (p-tau) in patients’ plasma of 22 AD, 23 MCI, and 9 negative control (NC) cases. Results: Plasma HCA was shown to be very high in areas under the receiver operating characteristic curves (AUC), distinguished between MCI and NC; when 0.116μM was chosen as the analyte concentration cut-off, the sensitivity was 95.7% and the specificity was 70%. Conclusion: Our results suggest that plasma HCA may be a useful indicator as an early diagnostic marker for MCI. HCA seems to be upstream from neurodegeneration in the AD pathology because it is known that an overactive NMDA receptor promotes amyloid polymerization and tau phosphorylation in AD.

Neurobiological Highlights of Cognitive Impairment in Psychiatric Disorders

“…HCA exhibited very high brain toxicity at low concentrations and overactivated the NMDAR. HCA seemed to be upstream from neurodegeneration in the AD pathology because it was known that an overactive NMDAR promoted amyloid polymerization and tau phosphorylation in AD [247].…”

Homocysteinylation and Sulfhydration in Diseases

“…A preliminary study suggests that plasma HCA may be a useful indicator as an early diagnostic marker for mild cognitive impairment (MCI). HCA is possibly upstream from neurodegeneration in the Alzheimer’s disease pathology because it promotes amyloid polymerization and tau phosphorylation in AD [ 49 ]. Adequate vitamin B 6 , vitamin B 12 , and folate intakes were significantly associated with better cognitive reserve by affecting methylation levels of specific redox-related genes [ 50 ].…”

Hyperhomocysteinemia: Metabolic Role and Animal Studies with a Focus on Cognitive Performance and Decline—A Review

“…Furthermore, investigations at ionotropic NMDA and metabotropic glutamate receptors revealed that ROS are produced to a higher extent by HCA than by HCys [128]. In a recent human study, Hasegawa and colleagues considered HCA as an early diagnostic marker of mild cognitive impairment and as more relevant than HCys in this context [129]. Earlier, it has been shown that treatment with an anti-HCA antibody attenuated cognitive impairment in the 3xTg-AD mouse model [130].…”