Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease: Current Evidence and Future Perspectives

McGrowder, Donovan; Miller, Fabian; Vaz, Kurt; Nwokocha, Chukwuemeka R.; Wilson-Clarke, Cameil; Anderson-Cross, Melisa; Brown, Jabari; Anderson-Jackson, Lennox; Williams, L. A. D.; Latore, Lyndon; Thompson, Rory; Alexander-Lindo, Ruby

doi:10.3390/brainsci11020215

Cited by 73 publications

(55 citation statements)

References 451 publications

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“…Classical CSF biomarkers are useful in identifying the AD biochemical fingerprint in typical and atypical AD cases [27,28]. Their diagnostic performance has been validated in autopsy-proven cases [56].…”

Section: Discussionmentioning

confidence: 99%

“…For in vivo diagnosis, various biomarkers have been studied during the last 25 years, including cerebrospinal fluid (CSF) biomarkers [27]. Among these, three are considered as classical or "core" biomarkers for AD [28]: Aβ 42 , which is decreased in AD and is inversely related to amyloid plaque burden [29]; tau protein phosphorylated to a threonine residue at position 181 (τ P-181 ) which is increased in AD and it is considered as a marker of tangle formation [30]; total tau protein (τ T ) which is increased in AD and it is a nonspecific marker of neuronal and/or axonal loss [31].…”

Section: Introductionmentioning

confidence: 99%

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From Cerebrospinal Fluid Neurochemistry to Clinical Diagnosis of Alzheimer’s Disease in the Era of Anti-Amyloid Treatments. Report of Four Patients

et al. 2021

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Analysis of classical cerebrospinal fluid biomarkers, especially when incorporated in a classification/diagnostic system such as the AT(N), may offer a significant diagnostic tool allowing correct identification of Alzheimer’s disease during life. We describe four patients with more or less atypical or mixed clinical presentation, in which the classical cerebrospinal fluid biomarkers amyloid peptide with 42 and 40 amino acids (Aβ42 and Aβ40, respectively), phospho-tau (τP-181) and total tau (τΤ) were measured. Despite the unusual clinical presentation, the biomarker profile was compatible with Alzheimer’s disease in all four patients. The measurement of classical biomarkers in the cerebrospinal fluid may be a useful tool in identifying the biochemical fingerprints of Alzheimer’s disease, especially currently, due to the recent approval of the first disease-modifying treatment, allowing not only typical but also atypical cases to be enrolled in trials of such treatments.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

From Cerebrospinal Fluid Neurochemistry to Clinical Diagnosis of Alzheimer’s Disease in the Era of Anti-Amyloid Treatments. Report of Four Patients

et al. 2021

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“…During the last two decades, various CSF biomarkers have been developed for the (differential) diagnosis of AD [25,26]. With sensitivities and specificities approaching or exceeding 90%, they have been incorporated into various guidelines and diagnostic criteria for Alzheimer's disease [12,27,28].…”

Section: The Csf Alzheimer's Disease Profilementioning

confidence: 99%

Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease in the Era of Disease-Modifying Treatments

Paraskevas

Kapaki

2021

Brain Sciences

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Correct in vivo diagnosis of Alzheimer’s disease (AD) helps to avoid administration of disease-modifying treatments in non-AD patients, and allows the possible use of such treatments in clinically atypical AD patients. Cerebrospinal fluid (CSF) biomarkers offer a tool for AD diagnosis. A reduction in CSF β-amyloid (marker of amyloid plaque burden), although compatible with Alzheimer’s pathological change, may also be observed in other dementing disorders, including vascular cognitive disorders due to subcortical small-vessel disease, dementia with Lewy bodies and normal-pressure hydrocephalus. Thus, for the diagnosis of AD, an abnormal result of CSF β-amyloid may not be sufficient, and an increase in phospho-tau (marker of tangle pathology) is also required in order to confirm AD diagnosis in patients with a typical amnestic presentation and reveal underlying AD in patients with atypical or mixed and diagnostically confusing clinical presentations.

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“…Generally, fluids [8], such as blood [9], saliva [9], urine [10], and cerebrospinal fluid (CSF) [11] and brain imaging techniques, such as structural MRI [12] and PET [13] have been used to establish a disease diagnosis and predict disease outcomes. Although CSF analysis is key in AD diagnosis, the moderately invasive nature of CSF collection limits its widespread use in routine primary clinical care practice, as the procedure is rarely performed by general practitioners [14].…”

Section: Introductionmentioning

confidence: 99%

Brain-Derived Exosomal Proteins as Effective Biomarkers for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

2021

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Alzheimer’s disease (AD), a progressive neurodegenerative disease, affects approximately 50 million people worldwide, which warrants the search for reliable new biomarkers for early diagnosis of AD. Brain-derived exosomal (BDE) proteins, which are extracellular nanovesicles released by all cell lineages of the central nervous system, have been focused as biomarkers for diagnosis, screening, prognosis prediction, and monitoring in AD. This review focused on the possibility of BDE proteins as AD biomarkers. The articles published prior to 26 January 2021 were searched in PubMed, EMBASE, Web of Science, and Cochrane Library to identify all relevant studies that reported exosome biomarkers in blood samples of patients with AD. From 342 articles, 20 studies were selected for analysis. We conducted a meta-analysis of six BDE proteins and found that levels of amyloid-β42 (standardized mean difference (SMD) = 1.534, 95% confidence interval [CI]: 0.595–2.474), total-tau (SMD = 1.224, 95% CI: 0.534–1.915), tau phosphorylated at threonine 181 (SMD = 4.038, 95% CI: 2.312-5.764), and tau phosphorylated at serine 396 (SMD = 2.511, 95% CI: 0.795–4.227) were significantly different in patients with AD compared to those in control. Whereas, those of p-tyrosine-insulin receptor substrate-1 and heat shock protein 70 did not show significant differences. This review suggested that Aβ42, t-tau, p-T181-tau, and p-S396-tau could be effective in diagnosing AD as blood biomarkers, despite the limitation in the meta-analysis based on the availability of data. Therefore, certain BDE proteins could be used as effective biomarkers for AD.

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Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease: Current Evidence and Future Perspectives

Cited by 73 publications

References 451 publications

From Cerebrospinal Fluid Neurochemistry to Clinical Diagnosis of Alzheimer’s Disease in the Era of Anti-Amyloid Treatments. Report of Four Patients

From Cerebrospinal Fluid Neurochemistry to Clinical Diagnosis of Alzheimer’s Disease in the Era of Anti-Amyloid Treatments. Report of Four Patients

Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease in the Era of Disease-Modifying Treatments

Brain-Derived Exosomal Proteins as Effective Biomarkers for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

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