Alzheimer’s disease CSF biomarkers: clinical indications and rational use

Niemantsverdriet, Ellis; Valckx, S.; Bjerke, Maria; Engelborghs, Sebastiaan

doi:10.1007/s13760-017-0816-5

Cited by 99 publications

(92 citation statements)

References 85 publications

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“…In AD subjects, the CSF concentration of Aβ 42 decreases over time, while 181-phospho-tau and total tau concentrations increase, when compared to healthy controls (including patients with psychiatric disorders such as depression) [ 110 ]. CSF studies have shown that the combined measurement of CSF Aβ 42 , total tau, and 181-phospho-tau levels can diagnose AD [ 111 ] with a sensitivity and specificity reaching 92 and 89%, respectively [ 112 ]. Other studies have suggested an assay using Aβ 42 and T-tau levels can accurately discriminate AD from controls by means of a discrimination line, which has been validated in clinical practice [ 113 ] and in autopsy-confirmed patients, with sensitivity levels of 100% and specificity of 91% [ 114 ].…”

Section: Biomarkers: Preferably Peripheralmentioning

confidence: 99%

Alzheimer’s Disease: A Journey from Amyloid Peptides and Oxidative Stress, to Biomarker Technologies and Disease Prevention Strategies—Gains from AIBL and DIAN Cohort Studies

Martins

Villemagne

Sohrabi

et al. 2018

JAD

106

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Worldwide there are over 46 million people living with dementia, and this number is expected to double every 20 years reaching about 131 million by 2050. The cost to the community and government health systems, as well as the stress on families and carers is incalculable. Over three decades of research into this disease have been undertaken by several research groups in Australia, including work by our original research group in Western Australia which was involved in the discovery and sequencing of the amyloid-β peptide (also known as Aβ or A4 peptide) extracted from cerebral amyloid plaques. This review discusses the journey from the discovery of the Aβ peptide in Alzheimer’s disease (AD) brain to the establishment of pre-clinical AD using PET amyloid tracers, a method now serving as the gold standard for developing peripheral diagnostic approaches in the blood and the eye. The latter developments for early diagnosis have been largely achieved through the establishment of the Australian Imaging Biomarker and Lifestyle research group that has followed 1,100 Australians for 11 years. AIBL has also been instrumental in providing insight into the role of the major genetic risk factor apolipoprotein E ɛ4, as well as better understanding the role of lifestyle factors particularly diet, physical activity and sleep to cognitive decline and the accumulation of cerebral Aβ.

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Section: Biomarkers: Preferably Peripheralmentioning

confidence: 99%

Alzheimer’s Disease: A Journey from Amyloid Peptides and Oxidative Stress, to Biomarker Technologies and Disease Prevention Strategies—Gains from AIBL and DIAN Cohort Studies

Martins

Villemagne

Sohrabi

et al. 2018

JAD

106

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show abstract

“…Biomarkers have been incorporated into research diagnostic criteria for AD [ 12–14 ] and, although the clinical examination (including full neuropsychological evaluation) is still the basis for AD diagnosis [ 1 ], these biomarkers are being introduced in daily clinical practice as in vivo surrogate markers for the confirmation of AD neuropathology. The core CSF AD biomarkers increase the diagnostic accuracy for diagnosing AD (mainly in cases with atypical presentations), also in its prodromal phase (mild cognitive impairment (MCI) due to AD) [ 15, 16 ] and are able to differentiate between AD and psychiatric disorders [ 17 ]. The CSF biomarkers are useful to diagnose AD in patients with ambiguous clinical dementia diagnoses [ 4 ] and in cases with mixed brain pathology like AD with cerebrovascular disease [ 5, 18, 19 ].…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Biomarkers for Early and Differential Alzheimer’s Disease Diagnosis

Bjerke

Engelborghs

2018

JAD

Self Cite

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An accurate and early diagnosis of Alzheimer’s disease (AD) is important to select optimal patient care and is critical in current clinical trials targeting core AD neuropathological features. The past decades, much progress has been made in the development and validation of cerebrospinal fluid (CSF) biomarkers for the biochemical diagnosis of AD, including standardization and harmonization of (pre-) analytical procedures. This has resulted in three core CSF biomarkers for AD diagnostics, namely the 42 amino acid long amyloid-beta peptide (Aβ1-42), total tau protein (T-tau), and tau phosphorylated at threonine 181 (P-tau181). These biomarkers have been incorporated into research diagnostic criteria for AD and have an added value in the (differential) diagnosis of AD and related disorders, including mixed pathologies, atypical presentations, and in case of ambiguous clinical dementia diagnoses. The implementation of the CSF Aβ1-42/Aβ1-40 ratio in the core biomarker panel will improve the biomarker analytical variability, and will also improve early and differential AD diagnosis through a more accurate reflection of pathology. Numerous biomarkers are being investigated for their added value to the core AD biomarkers, aiming at the AD core pathological features like the amyloid mismetabolism, tau pathology, or synaptic or neuronal degeneration. Others aim at non-AD neurodegenerative, vascular or inflammatory hallmarks. Biomarkers are essential for an accurate identification of preclinical AD in the context of clinical trials with potentially disease-modifying drugs. Therefore, a biomarker-based early diagnosis of AD offers great opportunities for preventive treatment development in the near future.

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“…Recently, cerebrospinal fluid (CSF) Aβ was suggested as an alternative biomarker for the amyloid concentration measurement by the 2018 revision of AD diagnostic criteria by National Institute on Aging and Alzheimer's Association (NIA-AA) [5][6][7][8]. Measurements of CSF Aβ show high diagnostic accuracy [9,10]. It is notable that, while Aβ concentration increase and soluble oligomers and insoluble plaques build up in the brain, the alteration of Aβ levels in CSF shows a proportionally inverse behavior.…”

Section: Introductionmentioning

confidence: 99%

Alterations of aqueous humor Aβ levels in Aβ-infused and transgenic mouse models of Alzheimer disease

Kwak

Koh

et al. 2020

PLoS ONE

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Alzheimer's disease (AD) is an ageing-related neurodegenerative disease characterized and diagnosed by deposition of insoluble amyloid-β (Aβ) plaques in the brain. The plaque accumulation in the brain directly affects reduced levels of Aβ in cerebrospinal fluid (CSF) and blood, as Aβ can freely transport the blood-brain barrier, and clinical investigations have suggested these two biofluids as promising samples for in vitro diagnosis. Given that the human eye structurally resembles the brain and Aβ accumulation often observed in the ocular region of AD patients, in this study, we examined aqueous humor Aβ as another possible surrogate biomarker. First, using the acute Aβ-infused AD mouse model by injecting Aβ to the CSF in intracerebroventricular region of normal ICR mice, we investigated whether Aβ concentration in the aqueous humor in AD models is positively correlated with the concentration in the CSF. Then, we examined the correlation of aqueous humor Aβ levels with increased plaque deposition in the brain and reduced Aβ levels in both CSF and blood in adult and aged 5XFAD Alzheimer transgenic mice. Collectively, the synthetic Aβ injected into CSF immediately migrate to the aqueous humor, however, the age-dependently reducing pattern of Aβ levels in CSF and blood was not observed in the aqueous humor.

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Alzheimer’s disease CSF biomarkers: clinical indications and rational use

Cited by 99 publications

References 85 publications

Alzheimer’s Disease: A Journey from Amyloid Peptides and Oxidative Stress, to Biomarker Technologies and Disease Prevention Strategies—Gains from AIBL and DIAN Cohort Studies

Alzheimer’s Disease: A Journey from Amyloid Peptides and Oxidative Stress, to Biomarker Technologies and Disease Prevention Strategies—Gains from AIBL and DIAN Cohort Studies

Cerebrospinal Fluid Biomarkers for Early and Differential Alzheimer’s Disease Diagnosis

Alterations of aqueous humor Aβ levels in Aβ-infused and transgenic mouse models of Alzheimer disease

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