Amyloid-PET and 18F-FDG-PET in the diagnostic investigation of Alzheimer's disease and other dementias

Chételat, Gaël; Arbizu, Javier; Barthel, Henryk; Garibotto, Valentina; Law, Ian; Morbelli, Silvia; Giessen, Elsmarieke van de; Agosta, Federica; Barkhof, Frederik; Brooks, David J.; Carrillo, María C.; Dubois, Bruno; Fjell, Anders M.; Frisoni, Giovanni B.; Hansson, Oskar; Herholz, Karl; Hutton, Brian F.; Jack, Clifford R.; Lammertsma, Adriaan A.; Landau, Susan; Minoshima, Satoshi; Nobili, Flavio; Nordberg, Agneta; Ossenkoppele, Rik; Oyen, W.J.G.; Perani, Daniela; Rabinovici, Gil D.; Scheltens, Philip; Villemagne, Victor L.; Zetterberg, Henrik; Drzezga, Alexander

doi:10.1016/s1474-4422(20)30314-8

Cited by 358 publications

(325 citation statements)

References 96 publications

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“…As the disease progresses, neuronal networks gradually switch to hypoactivity in AD during memory encoding (Celone et al, 2006;Persson et al, 2008;Reiman et al, 2012). Although there is currently many different compounds such as the Pittsburgh Compound B that can efficiently detect Aβ plaques in the brain using imaging techniques (Chetelat et al, 2020), the level of soluble Aβo cannot yet be directly measured in the brain of live patients. Although we know that the level of soluble Aβo begin to increase in the brain ∼10-15 years before any clinical symptoms of AD (Cline et al, 2018), it still need to be established if the hyperactivity observed in early AD patients is induced, at least partly, by this progressive accumulation of soluble Aβo in the brain as shown in vitro and in animal models.…”

Section: Neuronal Network Hyperactivity In Humansmentioning

confidence: 99%

Hyperactivity Induced by Soluble Amyloid-β Oligomers in the Early Stages of Alzheimer's Disease

Hector

Brouillette

2021

Front. Mol. Neurosci.

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Soluble amyloid-beta oligomers (Aβo) start to accumulate in the human brain one to two decades before any clinical symptoms of Alzheimer's disease (AD) and are implicated in synapse loss, one of the best predictors of memory decline that characterize the illness. Cognitive impairment in AD was traditionally thought to result from a reduction in synaptic activity which ultimately induces neurodegeneration. More recent evidence indicates that in the early stages of AD synaptic failure is, at least partly, induced by neuronal hyperactivity rather than hypoactivity. Here, we review the growing body of evidence supporting the implication of soluble Aβo on the induction of neuronal hyperactivity in AD animal models, in vitro, and in humans. We then discuss the impact of Aβo-induced hyperactivity on memory performance, cell death, epileptiform activity, gamma oscillations, and slow wave activity. We provide an overview of the cellular and molecular mechanisms that are emerging to explain how Aβo induce neuronal hyperactivity. We conclude by providing an outlook on the impact of hyperactivity for the development of disease-modifying interventions at the onset of AD.

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Section: Neuronal Network Hyperactivity In Humansmentioning

confidence: 99%

Hyperactivity Induced by Soluble Amyloid-β Oligomers in the Early Stages of Alzheimer's Disease

Hector

Brouillette

2021

Front. Mol. Neurosci.

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“…With several promising AD-modifying therapies in development, early detection of brain amyloidosis will be imperative for selecting and treating patients. Current AD diagnostic guidelines include tests that detect the presence of brain amyloid-β (Aβ) plaques using either amyloid PET imaging or low cerebrospinal fluid (CSF) Aβ42 levels or Aβ42/40 ratio; biomarkers for dysregulated Aβ metabolism and plaque formation [4][5][6][7][8][9][10]. Although amyloid PET imaging and CSF biomarkers have significantly improved the detection of brain amyloidosis, there is still a critical need for safe, lower cost, less resource-intensive, broadly available, blood-based biomarkers that identify the presence or absence of brain amyloid plaques.…”

Section: Introductionmentioning

confidence: 99%

A blood-based diagnostic test incorporating plasma Aβ42/40 ratio, ApoE proteotype, and age accurately identifies brain amyloid status: findings from a multi cohort validity analysis

West¹,

Kirmess²,

Meyer³

et al. 2021

Mol Neurodegeneration

146

145

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Background The development of blood-based biomarker tests that are accurate and robust for Alzheimer’s disease (AD) pathology have the potential to aid clinical diagnosis and facilitate enrollment in AD drug trials. We developed a high-resolution mass spectrometry (MS)-based test that quantifies plasma Aβ42 and Aβ40 concentrations and identifies the ApoE proteotype. We evaluated robustness, clinical performance, and commercial viability of this MS biomarker assay for distinguishing brain amyloid status. Methods We used the novel MS assay to analyze 414 plasma samples that were collected, processed, and stored using site-specific protocols, from six independent US cohorts. We used receiver operating characteristic curve (ROC) analyses to assess assay performance and accuracy for predicting amyloid status (positive, negative, and standard uptake value ratio; SUVR). After plasma analysis, sites shared brain amyloid status, defined using diverse, site-specific methods and cutoff values; amyloid PET imaging using various tracers or CSF Aβ42/40 ratio. Results Plasma Aβ42/40 ratio was significantly (p < 0.001) lower in the amyloid positive vs. negative participants in each cohort. The area under the ROC curve (AUC-ROC) was 0.81 (95% CI = 0.77–0.85) and the percent agreement between plasma Aβ42/40 and amyloid positivity was 75% at the optimal (Youden index) cutoff value. The AUC-ROC (0.86; 95% CI = 0.82–0.90) and accuracy (81%) for the plasma Aβ42/40 ratio improved after controlling for cohort heterogeneity. The AUC-ROC (0.90; 95% CI = 0.87–0.93) and accuracy (86%) improved further when Aβ42/40, ApoE4 copy number and participant age were included in the model. Conclusions This mass spectrometry-based plasma biomarker test: has strong diagnostic performance; can accurately distinguish brain amyloid positive from amyloid negative individuals; may aid in the diagnostic evaluation process for Alzheimer’s disease; and may enhance the efficiency of enrolling participants into Alzheimer’s disease drug trials.

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“…[50][51][52] In general, the use of neurological imaging has been limited within community owing to the high analytical cost and operational, and a poor understanding of amyloid burden relationship with cognitive dysfunction. 51,[53][54][55][56] Instead, immunoassay method (i.e., enzyme-linked immunosorbent assay (ELISA)) has been a plausible choice for the clinical diagnosis of Ab. ELISA is the gold standard immunoassay for CSF Ab (42) detection and is the most frequently used diagnostic method in AD.…”

Section: Biomarkers As Crucial Target For Biosensor Systemmentioning

confidence: 99%

Clinically oriented Alzheimer's biosensors: expanding the horizons towards point-of-care diagnostics and beyond

et al. 2021

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Amyloid-PET and 18F-FDG-PET in the diagnostic investigation of Alzheimer's disease and other dementias

Cited by 358 publications

References 96 publications

Hyperactivity Induced by Soluble Amyloid-β Oligomers in the Early Stages of Alzheimer's Disease

Hyperactivity Induced by Soluble Amyloid-β Oligomers in the Early Stages of Alzheimer's Disease

A blood-based diagnostic test incorporating plasma Aβ42/40 ratio, ApoE proteotype, and age accurately identifies brain amyloid status: findings from a multi cohort validity analysis

Clinically oriented Alzheimer's biosensors: expanding the horizons towards point-of-care diagnostics and beyond

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