Molecular imaging and fluid biomarkers of Alzheimer’s disease neuropathology: an opportunity for integrated diagnostics

Garibotto, Valentina; Boccardi, Marina; Chiti, Arturo; Frisoni, Giovanni B.

doi:10.1007/s00259-020-05116-y

Cited by 6 publications

(7 citation statements)

References 19 publications

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“…The screening strategy we suggest here could be implemented in clinical practice by performing plasma assessment in patients for whom an investigation of amyloid, tau and neurodegeneration statuses is considered appropriate. Patients with values below or above the thresholds for a sensitivity and specificity of 95% could be considered classifiable with a relatively high confidence, while others should be addressed for further investigation using traditional biomarkers in an integrated diagnostic approach 35…”

Section: Discussionmentioning

confidence: 99%

“…Patients with values below or above the thresholds for a sensitivity and specificity of 95% could be considered classifiable with a relatively high confidence, while others should be addressed for further investigation using traditional biomarkers in an integrated diagnostic approach. 35 …”

Section: Discussionmentioning

confidence: 99%

“…below or above the thresholds for a sensitivity and specificity of 95% could be considered classifiable with a relatively high confidence, while others should be addressed for further investigation using traditional biomarkers in an integrated diagnostic approach. 35 Before its clinical implementation, however, three main achievements should be fulfilled. (1) The test-retest reliability of the test should be evaluated systematically for all biomarkers and combinations thereof.…”

Section: Neurodegenerationmentioning

confidence: 99%

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Plasma biomarkers for Alzheimer’s disease: a field-test in a memory clinic

Altomare

Stampacchia

Ribaldi

et al. 2023

J Neurol Neurosurg Psychiatry

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BackgroundThe key Alzheimer’s disease (AD) biomarkers are traditionally measured with techniques/exams that are either expensive (amyloid-positron emission tomography (PET) and tau-PET), invasive (cerebrospinal fluid Aβ42and p-tau181), or poorly specific (atrophy on MRI and hypometabolism on fluorodeoxyglucose-PET). Recently developed plasma biomarkers could significantly enhance the efficiency of the diagnostic pathway in memory clinics and improve patient care. This study aimed to: (1) confirm the correlations between plasma and traditional AD biomarkers, (2) assess the diagnostic accuracy of plasma biomarkers as compared with traditional biomarkers, and (3) estimate the proportion of traditional exams potentially saved thanks to the use of plasma biomarkers.MethodsParticipants were 200 patients with plasma biomarkers and at least one traditional biomarker collected within 12 months.ResultsOverall, plasma biomarkers significantly correlated with biomarkers assessed through traditional techniques: up tor=0.50 (p<0.001) among amyloid,r=0.43 (p=0.002) among tau, andr=−0.23 (p=0.001) among neurodegeneration biomarkers. Moreover, plasma biomarkers showed high accuracy in discriminating the biomarker status (normal or abnormal) determined by using traditional biomarkers: up to area under the curve (AUC)=0.87 for amyloid, AUC=0.82 for tau, and AUC=0.63 for neurodegeneration status. The use of plasma as a gateway to traditional biomarkers using cohort-specific thresholds (with 95% sensitivity and 95% specificity) could save up to 49% of amyloid, 38% of tau, and 16% of neurodegeneration biomarkers.ConclusionThe implementation of plasma biomarkers could save a remarkable proportion of more expensive traditional exams, making the diagnostic workup more cost-effective and improving patient care.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Neurodegenerationmentioning

confidence: 99%

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Plasma biomarkers for Alzheimer’s disease: a field-test in a memory clinic

Altomare

Stampacchia

Ribaldi

et al. 2023

J Neurol Neurosurg Psychiatry

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“…In a recent commentary, Garibotto et al suggested that molecular imaging and fluid biomarkers provide an opportunity for integrated diagnosis of AD. The combination of different sources of information could potentially provide additional diagnostic value by leveraging the strengths and weaknesses of both techniques [25].…”

Section: Introductionmentioning

confidence: 99%

Perfusion Imaging and Inflammation Biomarkers Provide Complementary Information in Alzheimer’s Disease

Michopoulou,

Prosser,

Dickson

et al. 2023

JAD

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Background: Single photon emission tomography (SPECT) can detect early changes in brain perfusion to support the diagnosis of dementia. Inflammation is a driver for dementia progression and measures of inflammation may further support dementia diagnosis. Objective: In this study, we assessed whether combining imaging with markers of inflammation improves prediction of the likelihood of Alzheimer’s disease (AD). Methods: We analyzed 91 participants datasets (Institutional Ethics Approval 20/NW/0222). AD biomarkers and markers of inflammation were measured in cerebrospinal fluid. Statistical parametric mapping was used to quantify brain perfusion differences in perfusion SPECT images. Logistic regression models were trained to evaluate the ability of imaging and inflammation markers, both individually and combined, to predict AD. Results: Regional perfusion reduction in the precuneus and medial temporal regions predicted Aβ42 status. Increase in inflammation markers predicted tau and neurodegeneration. Matrix metalloproteneinase-10, a marker of blood-brain barrier regulation, was associated with perfusion reduction in the right temporal lobe. Adenosine deaminase, an enzyme involved in sleep homeostasis and inflammation, was the strongest predictor of neurodegeneration with an odds ratio of 10.3. The area under the receiver operator characteristic curve for the logistic regression model was 0.76 for imaging and 0.76 for inflammation. Combining inflammation and imaging markers yielded an area under the curve of 0.85. Conclusions: Study results showed that markers of brain perfusion imaging and markers of inflammation provide complementary information in AD evaluation. Inflammation markers better predict tau status while perfusion imaging measures represent amyloid status. Combining imaging and inflammation improves AD prediction.

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“…Thus, we might expect soon their introduction into clinical practice [10]. However, even when they will be available, it is most likely that a two-step procedure will be adopted, with a blood-based screening followed by a confirmation with a more accurate diagnostic strategy, presumably imaging, in an integrated diagnostic approach [11]. Finally, as the approval of the drug is based on the ability of the drug to reduce amyloid deposits, it might be expected that imaging, the only method allowing a measurement of brain amyloid load, will have a role in treatment monitoring.…”

mentioning

confidence: 99%

The approval of a disease-modifying treatment for Alzheimer’s disease: impact and consequences for the nuclear medicine community

Garibotto

Albert

Barthel

et al. 2021

Eur J Nucl Med Mol Imaging

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drug against Alzheimer's disease (AD), aducanumab (Aduhelm™), has been approved in the USA by the Food and Drug Administration (FDA).This event already has had a major impact, as shown by the storm of commentaries, both in favor and against it, in journals and social media before and after its disclosure. Its impact is linked to a number of factors: AD is a devastating and incurable disease with a dramatic toll on both patients and their families; Aducanumab is the first approved drug that was tested for its ability to influence the course of the disease (disease-modifying drug) and not only to treat This article is part of the Topical Collection on Neurology

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Molecular imaging and fluid biomarkers of Alzheimer’s disease neuropathology: an opportunity for integrated diagnostics

Cited by 6 publications

References 19 publications

Plasma biomarkers for Alzheimer’s disease: a field-test in a memory clinic

Plasma biomarkers for Alzheimer’s disease: a field-test in a memory clinic

Perfusion Imaging and Inflammation Biomarkers Provide Complementary Information in Alzheimer’s Disease

The approval of a disease-modifying treatment for Alzheimer’s disease: impact and consequences for the nuclear medicine community

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