Blood Biomarkers in Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that affects millions of people worldwide. The characteristic pathological manifestation of AD includes the deposition of extracellular insoluble β amyloid plaques and intracellular neurofibrillary tangles formed from hyperphosphorylated tau protein. Cost effective and minimally invasive peripheral blood-based biomarkers are critical for early AD diagnosis. Currently, the plasma based two fraction of β amyloid peptide ratio (Aβ42/40) and phosphorylated tau (p-tau) are considered as blood-based biomarkers for AD diagnosis. Recent research indicates that oxidative stress (OS) occurs prior to amyloid plaque (Aβ) formation and abnormal tau phosphorylation in AD. The imbalance of the master antioxidant, glutathione (GSH), and prooxidants (iron, zinc, and copper)�plays a crucial role in AD neurodegeneration. We present peripheral blood-based OS related biomarkers that are mechanistically involved in the disease process and may serve as a novel screening tool for early detection of AD onset. This OS based approach may also provide a quick and cost efficient method to monitor the effects of disease-modifying therapies in AD clinical trials.

Pro-Oxidants and Antioxidants Imbalance in Alzheimer’s Disease

“…A transgenic AD mice model study also showed that GSH depletion precedes amyloid plaque formation [13]. Significant depletion of plasma GSH from mild cognitive impairment (MCI) subjects has also been reported in a longitudinal study [14,15]. This supplemental issue of the Journal of Alzheimer's Disease highlights OS-based AD research from various laboratories around the globe.…”

“…Deferiprone) in randomized clinical trials (RCT) involving Prodromal and mild AD patients for cognitive preservation is awaited. The efficacy of the RCT can be monitored from the analysis of plasma GSH and serum iron levels from the trial participants [14]. These valuable data can be kept in a dedicated database called SWADESH [29].…”

Unleashing the power of chlorogenic acid: exploring its potential in nutrition delivery and the food industry

“…Growing evidence suggests that enhancing Aβ peptide clearance contributes to preventing AD. 59,60 In a study by Gao et al , the molecular mechanisms of CGA were explored using a model of Aβ25–35-induced APP/PS1 transgenic mice with SH-SY5Y neuronal damage and cognitive impairment. The findings indicate that CGA significantly enhances spatial memory in APP/PS1 mice, mitigates neuronal damage, inhibits autophagy, and, by activating the mTOR/TFEB signaling pathway, restores brain autophagic flux in APP/PS1 mice, thereby alleviating cognitive impairment.…”

Plasma GFAP, NfL and pTau 181 detect preclinical stages of dementia

“…Biomarkers analyzed on blood sample are desirable as easily accessible and non-invasive tools. Plasma biomarkers are promising candidates for the early diagnosis of AD, tied to the biological β Amyloid (A) deposition, pathologic Tau (T), and Neurodegeneration (N) [ATN] framework ( 4 , 6 – 8 ). Recently, plasma glial fibrillary acidic protein (GFAP), an intermediate filament protein of astrocytes, has been demonstrated to be associated with brain amyloid status and the development of clinical AD and cognitive decline ( 9 , 10 ).…”