Potential fluid biomarkers for pathological brain changes in Alzheimer's disease: Implication for the screening of cognitive frailty

Abstract

Cognitive frailty (CF) overlaps with early neuropathological alterations associated with aging-related major neurocognitive disorders, including Alzheimer's disease (AD). Fluid biomarkers for these pathological brain alterations allow for early diagnosis in the preclinical stages of AD, and for objective prognostic assessments in clinical intervention trials. These biomarkers may also be helpful in the screening of CF. The present study reviewed the literature and identified systematic reviews of cohort studies and other authoritative reports. The selection criteria for potentially suitable fluid biomarkers included: i) Frequent use in studies of fluid-derived markers and ii) evidence of novel measurement techniques for fluid-derived markers. The present study focused on studies that assessed these biomarkers in AD, mild cognitive impairment and non-AD demented subjects. At present, widely used fluid biomarkers include cerebrospinal fluid (CSF), total tau, phosphorylated tau and amyloid-β levels. With the development of novel measurement techniques and improvements in understanding regarding the mechanisms underlying aging-related major neurocognitive disorders, numerous novel biomarkers associated with various aspects of AD neuropathology are being explored. These include specific measurements of Aβ oligomer or monomer forms, tau proteins in the peripheral plasma and CSF, and novel markers of synaptic dysfunction, neuronal damage and apoptosis, neuronal activity alteration, neuroinflammation, blood brain barrier dysfunction, oxidative stress, metabolites, mitochondrial function and aberrant lipid metabolism. The proposed panels of fluid biomarkers may be useful in the early diagnosis of AD, prediction of the progression of AD from preclinical stages to the dementia stage, and the differentiation of AD from non-AD dementia. In combination with physical frailty, the present study surmised that these biomarkers may also be used as biomarkers for CF, thus contribute to discovering causes and informing interventions for cognitive impairment in individuals with CF.

Identification of Blood Biomarkers for Alzheimer's Disease Through Computational Prediction and Experimental Validation

“…In addition, pathway enrichment analysis was conducted on these genes and showed that focal adhesion, TGF-β signaling pathway, and MAPK signaling pathway were significantly enriched by up-regulated genes, and synapse transmission, neuronal system, and calcium signaling pathway were significantly enriched by down-regulated genes [complete list shown in our previous study (27)]. These pathways are consistent with previous observations that AD is associated with neuronal damage and apoptosis, synaptic dysfunction, neuronal activity alteration, blood brain barrier dysfunction, neuro inflammation, oxidative stress, mitochondrial function and aberrant lipid metabolism (28). Therefore, these differentially expressed genes are speculated to be associated with AD pathogenesis.…”

Urinary Apolipoprotein C3 Is a Potential Biomarker for Alzheimer’s Disease

“…This makes urine ideal for biomarker discovery and screening tests [ 5 ]. However, studies on urinary AD biomarkers are limited [ 6 ], with only a few reports on protein biomarkers [ 7 , 8 ].…”

Functional analyses of major cancer-related signaling pathways in Alzheimer's disease etiology

“…Recently, biomarkers derived from cerebrospinal fluid (CSF) and peripheral blood have been developed for the purpose of early AD symptom detection. Among which, CSF-based biomarkers have been designed for AD detection dependent on the alteration of neuron pathological lesions, including total tau protein (T-tau, reflecting the intensity of neuro axonal degeneration), phosphorylated tau (P-tau, correlating with tangle pathology) and the ratio of Aβ42/40 (correlating inversely with the plaque pathology) as previously reported [23, 24]. …”