Cerebrospinal fluid biomarkers of Alzheimer’s disease

Abstract

Alzheimer's disease (AD) is a fatal neurodegenerative disorder that takes about a decade to develop, making early diagnosis possible. Clinically, the diagnosis of AD is complicated, costly, and inaccurate, so it is urgent to fi nd specifi c biomarkers. Due to its multifactorial nature, a panel of biomarkers for the multiple pathologies of AD, such as cerebral amyloidogenesis, neuronal dysfunction, synapse loss, oxidative stress, and infl ammation, are most promising for accurate diagnosis. Highly sensitive and high-throughput proteomic techniques can be applied to develop a panel of novel biomarkers for AD. In this review, we discuss the metabolism and diagnostic performance of the well-established core candidate cerebrospinal fl uid (CSF) biomarkers (β-amyloid, total tau, and hyperphosphorylated tau). Meanwhile, novel promising CSF biomarkers, especially those identifi ed by proteomics, updated in the last fi ve years are also extensively discussed. Furthermore, we provide perspectives on how biomarker discovery for AD is evolving.Keywords: Alzheimer's disease; biomarker; cerebrospinal fl uid; β-amyloid; tau; proteomics ·Review· Introduction Alzheimer's disease (AD) is becoming more prevalent due to the increasing population of people aged over 65 [1] .It is estimated that it will affect 66 million by 2030 and 115 million by 2050 worldwide if no effective therapeutic strategies are found [2] . Clinically, AD is characterized by cognitive impairment, progressive disturbance of daily activities, many neuropsychiatric symptoms, and behavioral deterioration [3][4][5][6][7][8] . Pathologically, it is characterized by deposition of extracellular neuritic plaques composed of β-amyloid (Aβ) [9] and intracellular neurofibrillary tangles (NFTs) consisting of a hyperphosphorylated form of the microtubule-associated protein tau [10][11][12] . Besides, loss of neurons and synapses is also a pathological hallmark of AD [13][14][15] . The worldwide cost of dementia is huge and expected to skyrocket in the next few years. AD may become one of the most marked social, health, and economic challenges in the twenty-fi rst century [16] .Clinically, the procedure for the diagnosis of AD is diffi cult and complex. Neuropsychological tests, such as the mini-mental state examination, magnetic resonance imaging of hippocampal volume, and clinical assessment, are used to aid in diagnosis. However, a defi nitive diagnosis of AD requires confirmation at autopsy. It is estimated to take 8-10 years or longer before mild cognitive impairment (MCI) develops into AD [17,18] . Meanwhile, intervention therapies work most effectively in the early stage of AD. Thus, it is urgent and feasible to seek novel specifi c biomarkers to aid in diagnosis and the evaluation of treatments [19] . Surrounding the brain and spinal cord, cerebrospinal fluid (CSF) is an ideal source refl ecting biochemical changes in the brain of the AD patient [20] . Extensive studies have focused on seeking AD biomarkers in CSF.A comprehensive search of the Web of Science (Janua...

Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms

“…Nevertheless, neuroinflammation and oxidative stress have received increasing attention as accumulating evidence suggests their involvement in its development [2,3]. Activation of microglia, the brain-specific macrophages, has been reported in both AD patients and animal models [4], accompanied by an activated complement system [5] and increased levels of chemokines and cytokines [6,7]. In addition, the protective effects of non-steroidal antiinflammatory drugs against AD risk [8] further support the neuroinflammation hypothesis of AD.…”

Bayesian Graphical Network Analyses Reveal Complex Biological Interactions Specific to Alzheimer's Disease

“…However, the ‘gold standard’ peripheral biomarker for AD that will reliably identify individuals on a path toward AD, or even correlate with promising, but invasive and impractical cerebrospinal fluid (CSF) [2] and positron emission tomography (PET) biomarkers [3], is yet to emerge. Nevertheless, much hope is dedicated to the idea that such a marker does exist in the periphery.…”

Evaluation of Different Factors Leading to the Genesis of Alzheimer’s Disease: Research Proposal on Dementia

“…The biomarkers that have been strongly associated with the diagnosis of Alzheimer's are Aβ-40, Aβ-42 and tau proteins [30][31][32][33][34][35]. All these biomarkers have been isolated from the cerebrospinal fluid and provide a fair estimation of Alzheimer's disease.…”

“…Hence, the focus for diagnosis of Alzheimer's has been shifted towards less invasive procedures. Assay of blood-based biomarkers has received great attention for the diagnosis and detection of Alzheimer's [30][31][32]. Studies have indicated that the plasma concentrations of Aβ-40 and Aβ-42 are high in individuals suffering from Alzheimer's.…”

“…These biomarkers include conformational alterations in p53 protein, IL-1 receptor antagonist, C-reactive protein, alpha-1 chymotrypsin and tumor necrosis factor-alpha [31,32]. Studies have suggested that the etiology Alzheimer's is extremely complex and diagnosis should not be based on any one specific biomarker [30][31][32][33][34][35]. Single marker assays are either ineffective or inappropriate for diagnosing the presence of Alzheimer's disease in an individual.…”