How many biomarkers to discriminate neurodegenerative dementia?

Sancesario, Giulia Maria; Bernardini, Sergio

doi:10.3109/10408363.2015.1051658

Cited by 17 publications

(13 citation statements)

References 171 publications

(189 reference statements)

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“…In these clinical settings of PD and DLB, the presence of a biomarker that indicates that abnormal pathological forms of a αSyn are present would improve diagnostic accuracy not only for prognostic purposes but also for cohort selection in disease-modifying clinical trials for PD. Attempts to determine if cerebrospinal fluid (CSF) levels of total, phosphorylated or oligomeric a-syn are diagnostically useful have been variable and controversial between studies [reviewed in [ 27 ]], and the diagnostic utility of immunoassays for these forms of αSyn in CSF remains unclear [ 21 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC

Groveman

Orrú

Hughson

et al. 2018

acta neuropathol commun

279

371

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The diagnosis and treatment of synucleinopathies such as Parkinson disease and dementia with Lewy bodies would be aided by the availability of assays for the pathogenic disease-associated forms of α-synuclein (αSynD) that are sufficiently sensitive, specific, and practical for analysis of accessible diagnostic specimens. Two recent αSynD seed amplification tests have provided the first prototypes for ultrasensitive and specific detection of αSynD in patients’ cerebrospinal fluid. These prototypic assays require 5–13 days to perform. Here, we describe an improved α-synuclein real time quaking-induced conversion (αSyn RT-QuIC) assay that has similar sensitivity and specificity to the prior assays, but can be performed in 1–2 days with quantitation. Blinded analysis of cerebrospinal fluid from 29 synucleinopathy cases [12 Parkinson’s and 17 dementia with Lewy bodies] and 31 non-synucleinopathy controls, including 16 Alzheimer’s cases, yielded 93% diagnostic sensitivity and 100% specificity for this test so far. End-point dilution analyses allowed quantitation of relative amounts of αSynD seeding activity in cerebrospinal fluid samples, and detection in as little as 0.2 μL. These results confirm that αSynD seeding activity is present in cerebrospinal fluid. We also demonstrate that it can be rapidly detected, and quantitated, even in early symptomatic stages of synucleinopathy.Electronic supplementary materialThe online version of this article (10.1186/s40478-018-0508-2) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC

Groveman

Orrú

Hughson

et al. 2018

acta neuropathol commun

279

371

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“…In 2011, the recommendation for AD diagnosis have been revised by both the International Working Group (IWG) (4) and the US National Institute on Aging-Alzheimer's Association (NIA-AA) (5-7). The new criteria abandon the old concept of AD dementia, based on the clinical assessment and autopsy confirmation, introducing a paradigm shift which points to early in vivo diagnosis of AD before development of dementia, thus representing a step forward from clinical-autoptic paradigm, registering the clinical consequences of completed pathological process to a clinical-biological paradigm, which emphasis on measurable in vivo evidences of developing AD pathology (8,9), which can be investigated by both CSF and topographical markers (assessed by PiB-PET and MRI).…”

Section: The Evolution Of the Diagnosis Of Alzheimer's Dementiamentioning

confidence: 99%

Diagnosis of neurodegenerative dementia: where do we stand, now?

Sancesario¹,

Bernardini²

2018

Ann. Transl. Med.

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After many years of large efforts made for understanding the pathogenesis of dementias, the early diagnosis of these degenerative diseases remains an open challenge. Alzheimer's disease (AD) represents the most common form of dementia, followed by Lewy body disease and frontotemporal degeneration. Actually, different pathological processes can determine similar and overlapping clinical syndrome. To detect in vivo the pathological process underlying progressive cognitive and behavior impairment, the Internationals guidelines recommend the use of biological and topographical markers, which can reflect neuropathological modifications in brain. In cerebrospinal fluid (CSF), decrease of amyloid beta 1-42 (Aβ42) and a low ratio of Aβ42 with amyloid beta 1-40 (Aβ42/Aβ40), together with the increase of both total tau protein (t-tau) and phosphorylated tau (p-tau), contribute to define the "Alzheimer's signature". This review points out on the evolution of the concept for early diagnosis of AD, and on the current use of CSF proteins for research purposes and in clinical setting. Then, we discuss the limitations and drawbacks in wide application of CSF biomarkers for diagnosing degenerative dementias, and on the role of laboratory medicine to convey these biomarkers from "research" toward "clinical practice".

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“…Currently, AD can be diagnosed with over 90% of confidence but with invasive and expensive tools based on cerebrospinal fluid (CSF) analysis and neuroimaging with positron emission tomography, with Pittsburgh compound-B radiotracer (PET/PiB) [126]. For this reason, the diagnosis is based on neuropsychological surveys and in the exclusion of other age-related dementias only when there is an advanced cognitive impairment [127]. The conclusive diagnosis of AD is only possible in autopsy with the presence of characteristic pathological brain lesions [125,127].…”

Section: Mitochondrial Dysfunction Can Help Us To Predict Ad?mentioning

confidence: 99%

“…For this reason, the diagnosis is based on neuropsychological surveys and in the exclusion of other age-related dementias only when there is an advanced cognitive impairment [127]. The conclusive diagnosis of AD is only possible in autopsy with the presence of characteristic pathological brain lesions [125,127].…”

Section: Mitochondrial Dysfunction Can Help Us To Predict Ad?mentioning

confidence: 99%

New Targets for Diagnosis and Treatment Against Alzheimer’s Disease: The Mitochondrial Approach

Pérez¹,

Jara²,

Muñoz‐Urrutia³

et al. 2016

Update on Dementia

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Alzheimer's disease (AD) is a neurodegenerative disorder and the most common form of dementia. AD is characterized by brain presence of senile plaques, which are formed by aggregates of Aβ peptide and neurofibrillary tangles (NFTs), formed by pathological forms of tau protein. Evidence suggests that these elements affect neurons compromising energy supply, antioxidant response and synaptic activity. AD principally affects the memory and cognitive functions of the patients, and currently, successful strategies for diagnosis and early treatment are lacking. In this scenario, accumulative evidence suggests that mitochondrial dysfunction precedes the establishment of tau and Aβ pathology and contributes to synaptic degeneration observed in AD. Therefore, reducing mitochondrial injury may have beneficial effects for neuronal dysfunction and cognitive decline observed in AD patients. Interestingly, the examination of peripheral cells from AD patients also presents mitochondrial dysfunction, suggesting that tracking these mitochondrial defects in peripheral cells could be a potential mechanism of early diagnosis of AD. In this chapter, we analyse current evidence that suggests that mitochondrial injury is an important factor in the pathogenesis of AD and how studying this process could reveal new strategies to mitigate neurodegeneration and to develop new diagnostic methods for an early detection of AD.

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How many biomarkers to discriminate neurodegenerative dementia?

Cited by 17 publications

References 171 publications

Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC

Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC

Diagnosis of neurodegenerative dementia: where do we stand, now?

New Targets for Diagnosis and Treatment Against Alzheimer’s Disease: The Mitochondrial Approach

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